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Sample records for buprenorphine

  1. Buprenorphine

    Directory of Open Access Journals (Sweden)

    Jaroslaw Mazurek

    2014-06-01

    Full Text Available In the crystal structure of a semi-synthetic opioid drug buprenorphine, C29H41NO4 {systematic name: (2S-2-[(5R,6R,7R,14S-9α-cyclopropylmethyl-3-hydroxy-6-methoxy-4,5-epoxy-6,14-ethanomorphinan-7-yl]-3,3-dimethylbutan-2-ol}, the cyclopropylmethyl group is disordered over two sites with an occupancy factor of 0.611 (3 for the major component. One of the hydroxy groups is involved in intramolecular O—H...O hydrogen bond. The other hydroxy group acts as a proton donor in an intermolecular O—H...O interaction that connects molecules into a zigzag chain along the b axis.

  2. Buprenorphine Buccal (chronic pain)

    Science.gov (United States)

    Buprenorphine (Belbuca) is used to relieve severe pain in people who are expected to need pain medication ... and who cannot be treated with other medications. Buprenorphine (Belbuca) should not be used to treat pain ...

  3. Buprenorphine Transdermal Patch

    Science.gov (United States)

    Buprenorphine patches are used to relieve severe pain in people who are expected to need pain medication ... Transdermal buprenorphine comes as a patch to apply to the skin. The patch is usually applied to the skin ...

  4. Continuous Perioperative Sublingual Buprenorphine.

    Science.gov (United States)

    Silva, Marcelina Jasmine; Rubinstein, Andrea

    2016-12-01

    Buprenorphine, a semisynthetic thebaine derivative, is a unique opioid, as it has activity at multiple receptors, including mu (partial agonist), kappa (antagonist), OLR-1 (agonist), and delta (antagonist). Because buprenorphine's pharmacology is relatively complex, misconceptions about its actions are common. Most other opioids act solely or predominately as full mu receptor agonists. Common practice at many institutions calls for the cessation of regular buprenorphine use 48-72 hours prior to surgery. This practice is based on three foundational theories that have come from scant data about the properties of buprenorphine: (1) that buprenorphine is only a partial mu agonist and therefore is not a potent analgesic; (2) because buprenorphine has a ceiling effect on respiratory depression, it also has a ceiling effect on analgesia; and (3) that buprenorphine acts as a "blockade" to the analgesic effects of other opiates when coadministered due to its strong binding affinity. However, several recent studies have called this practice into question. At our institution, we continue buprenorphine perioperatively, whenever possible, in order to provide superior pain control, discourage potentially problematic use and the more dangerous side effects of full mu agonist opiates, and avoid putting recovery at risk for those with opiate dependency issues. We present a unique case comparing two different outcomes for the same surgical course performed at two different times on the same chronic pain patient. These differences may be attributable to the variable of buprenorphine being present for one perioperative course and not the other. Pain control was easier to achieve, and functional recovery was greater when buprenorphine was maintained throughout the perioperative period when compared with using a full mu agonist opioid for chronic pain preoperatively. This is an outcome that much of the literature heretofore suggests would be unlikely. We review some aspects of

  5. Maternal Buprenorphine Maintenance and Lactation.

    Science.gov (United States)

    Jansson, Lauren M; Spencer, Nancy; McConnell, Krystle; Velez, Martha; Tuten, Michelle; Harrow, Cheryl A; Jones, Hendrée E; Swortwood, Madeleine J; Barnes, Allan J; Scheidweiler, Karl B; Huestis, Marilyn A

    2016-11-01

    In addition to the well-known benefits of human milk and breastfeeding for the mother and infant, breastfeeding may mitigate neonatal abstinence syndrome severity in prenatally opioid-exposed infants. However, lack of conclusive data regarding the extent of the presence of buprenorphine and active metabolites in human milk makes the recommendation of breastfeeding for buprenorphine-maintained women difficult for many providers. This study seeks to determine the concentrations of buprenorphine and its active metabolites (norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine-glucuronide) in human milk, maternal plasma, and infant plasma of buprenorphine-maintained women and their infants. Up to 10 buprenorphine-maintained women provided paired breast milk and plasma samples at 2, 3, 4, 14, and 30 days postdelivery, and 9 infants provided plasma samples on day 14 of life. All samples were analyzed via liquid chromatography tandem mass spectrometry to determine concentrations of buprenorphine, norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine-glucuronide by a fully validated method. Concentrations of buprenorphine and metabolites are low in human milk and maternal plasma. Breastfed infant plasma concentrations of buprenorphine were low or undetectable and metabolite concentrations undetectable at 14 days of infant age. There were significant correlations between maternal buprenorphine dose and maternal plasma and human milk buprenorphine concentrations. These data find low concentrations of buprenorphine and metabolites in human milk and lend support to the recommendation for lactation among stable buprenorphine-maintained women. However, the correlation between maternal dose and maternal plasma and human milk buprenorphine concentrations bears further study.

  6. Radioimmunoassay of buprenorphine

    Energy Technology Data Exchange (ETDEWEB)

    Bartlett, A.J.; Lloyd-Jones, J.G.; Rance, M.J.; Flockhart, I.R.; Dockray, G.J.; Bennett, M.R.D.

    1980-01-01

    Antisera to buprenorphine were obtained in rabbits immunised with 3-0-carboxymethylbuprenorphine and N-hemisuccinyl-norbuprenorphine conjugated to bovine serum albumin. Using the latter antiserum and tritium labelled buprenorphine a radioimmunoassay having good accuracy and precision was developed for concentrations as low as 50 picograms in 1 ml of plasma. The N-hemisuccinyl antiserum crossreacted with norbuprenorphine, and the 3-0-glucuronide conjugate with the 3-0-carboxy-methyl antiserum. Cross-reactivity of both antisera to other pharmacologically related compounds was negligible. The assay was employed to determine plasma buprenorphine concentration following its parenteral administration to dog and man.

  7. Buprenorphine and Buprenorphine/Naloxone Diversion, Misuse, and Illicit Use: An International Review

    OpenAIRE

    Yokell, Michael A.; Zaller, Nickolas D.; Green, Traci C.; Rich, Josiah D.

    2011-01-01

    The diversion, misuse, and non-medically supervised use of buprenorphine and buprenorphine/naloxone by opioid users are reviewed. Buprenorphine and buprenorphine/naloxone are used globally as opioid analgesics and in the treatment of opioid dependency. Diversion of buprenorphine and buprenorphine/naloxone represents a complex medical and social issue, and has been widely documented in various geographical regions throughout the world.

  8. Prior buprenorphine experience is associated with office-based buprenorphine treatment outcomes

    Science.gov (United States)

    Cunningham, Chinazo O.; Roose, Robert J.; Starrels, Joanna L.; Giovanniello, Angela; Sohler, Nancy L.

    2013-01-01

    Objectives As buprenorphine treatment and illicit buprenorphine use increase, many patients seeking buprenorphine treatment will have had prior experience with buprenorphine. Little evidence is available to guide optimal treatment strategies for patients with prior buprenorphine experience. We examined whether prior buprenorphine experience was associated with treatment retention and opioid use. We also explored whether type of prior buprenorphine use (prescribed or illicit use) was associated with these treatment outcomes. Methods We analyzed interview and medical record data from a longitudinal cohort study of 87 individuals who initiated office-based buprenorphine treatment. We examined associations between prior buprenorphine experience and 6-month treatment retention using logistic regression models, and prior buprenorphine experience and any self-reported opioid use at 1, 3, and 6 months using non-linear mixed models. Results Most (57.4%) participants reported prior buprenorphine experience; of these, 40% used prescribed buprenorphine and 60% illicit buprenorphine only. Compared to buprenorphine-naïve participants, those with prior buprenorphine experience had better treatment retention (AOR=2.65, 95% CI=1.05–6.70). Similar associations that did not reach significance were found when exploring prescribed and illicit buprenorphine use. There was no difference in opioid use when comparing participants with prior buprenorphine experience to those who were buprenorphine-naive (AOR=1.33, 95% CI=0.38–4.65). Although not significant, qualitatively different results were found when exploring opioid use by type of prior buprenorphine use (prescribed buprenorphine vs. buprenorphine-naïve, AOR=2.20, 95% CI=0.58–8.26; illicit buprenorphine vs. buprenorphine-naïve, AOR=0.47, 95% CI=0.07–3.46). Conclusions Prior buprenorphine experience was common and associated with better retention. Understanding how prior buprenorphine experience affects treatment outcomes

  9. [Buprenorphine abuse: high dose intravenous administration of buprenorphine].

    Science.gov (United States)

    Varescon, I; Vidal-Trécan, G; Nabet, N; Boissonnas, A

    2002-01-01

    In France, actually, around 70 000 drug addicts are treated with buprenorphine available as sublingual tablets. Clinical studies have demonstrated the clinical efficacity of buprenorphine for opiate addiction. But, it has been reported that some of them injected buprenorphine. Some inquiries have suggested measured with 10% to 40% injectors. To use buprenorphine tablets for injections have had heavy sanitary consequences (4). To know the use buprenorphine context in our population and to analyse the circumstances and outcomes of buprenorphine injection for drug addicts. In 1998-1999, we conducted a cross-sectional survey using a structured questionnaire. Information wax collected during a 30-minute face-to-face interview through an 69-item structured questionnaire administered by trained investigators. The questionnaire was composed of questions about social demographic data, the drugs taken before the first use of buprenorphine, the circumstances of the first buprenorphine experiment, the reasons for the first buprenorphine injection into drug addicts, the other substances used in the same time, the risks behaviors, the sensations seeking, the medical consequences. The questionnaire was first tested in a pilot study through ten patients. Drug addicts were followed-up in 8 drug abuse treatment centres among which 2 networks of general practitioners in Paris region, in Strasbourg region and in Nice region. The investigators were general practitioners, psychologists, psychiatrists, educators, nurses. All drugs addict which reported use buprenorphine were seen in treatment centre and were 18 years old or older, were eligible. Drugs addict with severe mental disorders, unable to answer the questions were excluded. Respondents received an assurance of confidentiality and informed consent was obtained. Standard descriptive statistics were used to analyse subjects characteristics: frequency, standard deviation. The study was funded by the Observatoire Français des

  10. Buprenorphine for managing opioid withdrawal.

    Science.gov (United States)

    Gowing, Linda; Ali, Robert; White, Jason M; Mbewe, Dalitso

    2017-02-21

    Managed withdrawal is a necessary step prior to drug-free treatment or as the endpoint of substitution treatment. To assess the effects of buprenorphine versus tapered doses of methadone, alpha 2 -adrenergic agonists, symptomatic medications or placebo, or different buprenorphine regimens for managing opioid withdrawal, in terms of the intensity of the withdrawal syndrome experienced, duration and completion of treatment, and adverse effects. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 11, 2016), MEDLINE (1946 to December week 1, 2016), Embase (to 22 December 2016), PsycINFO (1806 to December week 3, 2016), and the Web of Science (to 22 December 2016) and handsearched the reference lists of articles. Randomised controlled trials of interventions using buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha 2 -adrenergic agonists (clonidine or lofexidine), symptomatic medications or placebo, and different buprenorphine-based regimens. We used standard methodological procedures expected by Cochrane. We included 27 studies involving 3048 participants. The main comparators were clonidine or lofexidine (14 studies). Six studies compared buprenorphine versus methadone, and seven compared different rates of buprenorphine dose reduction. We assessed 12 studies as being at high risk of bias in at least one of seven domains of methodological quality. Six of these studies compared buprenorphine with clonidine or lofexidine and two with methadone; the other four studies compared different rates of buprenorphine dose reduction.For the comparison of buprenorphine and methadone in tapered doses, meta-analysis was not possible for the outcomes of intensity of withdrawal or adverse effects. However, information reported by the individual studies was suggestive of buprenorphine and methadone having similar capacity to

  11. Intravenous buprenorphine and norbuprenorphine pharmacokinetics in humans

    Science.gov (United States)

    Huestis, M.A.; Cone, E.J.; Pirnay, S.O.; Umbricht, A.; Preston, K.L.

    2013-01-01

    Background Prescribed sublingual (SL) buprenorphine is sometimes diverted for intravenous (IV) abuse, but no human pharmacokinetic data are available following high-dose IV buprenorphine. Methods Plasma was collected for 72 h after administration of placebo or 2, 4, 8, 12, or 16 mg IV buprenorphine in escalating order (single-blind, double-dummy) in 5 healthy male non-dependent opioid users. Buprenorphine and its primary active metabolite, norbuprenorphine, were quantified by liquid chromatography tandem mass spectrometry with limits of quantitation of 0.1 μg/L. Results Maximum buprenorphine concentrations (mean ± SE) were detected 10 min after 2, 4, 8, 12, 16 mg IV: 19.3±1.0, 44.5±4.8, 85.2±7.7, 124.6±16.6, and 137.7±18.8 μg/L, respectively. Maximum norbuprenorphine concentrations occurred 10–15 min (3.7±0.7 μg/L) after 16 mg IV administration. Conclusions Buprenorphine concentrations increased in a significantly linear dose-dependent manner up to 12 mg IV buprenorphine. Thus, previously demonstrated pharmacodynamic ceiling effects (over 2–16 mg) are not due to pharmacokinetic adaptations within this range, although they may play a role at doses higher than 12 mg. PMID:23246635

  12. Buprenorphine During Pregnancy Reduces Neonate Distress

    Science.gov (United States)

    ... and HIV; of experiencing pregnancy complications, including spontaneous abortion and miscarriages; and of having a child with ... health risks related to acquiring and abusing drugs. Therapeutic dosing with buprenorphine, as with methadone, avoids the ...

  13. [Breast feeding during methadon- and buprenorphin therapy].

    Science.gov (United States)

    Müller, M J; Lange, M; Paul, T; Seeliger, S

    2011-12-01

    The number of opiate addicted patients treated with opioid replacement therapy is continuously increasing. In Germany, 57.7% of these patients are treated with methadone and 18.6% with buprenorphine. This maintenance therapy provides several advantages while addicted pregnant women and their foetus have a high benefit from appropriate replacement therapy. However, the recommendations concerning breast feeding during an opioid replacement therapy are discussed controversially, because methadone as well as buprenorphine accumulate in breast milk. This accumulation might cause damages to the newborn's health; so, child benefits of breast feeding have to be balanced with possible health risks.This review provides an overview of a selective literature search based on the PubMed-database and german consensus recommendations. Used search terms included: (methadone*) AND (breastfeeding OR lactation), (methadone*) AND (human milk), (buprenorphine*) AND (breastfeeding OR lactation) and (buprenorphine*) AND (human milk).According to the available literature, addicted women, substinated with methadone or buprenorphine are allowed to breast feed their newborns. The advantages of breast feeding prevail the risks of an infant opiate intoxication caused by methadone or buprenorphine. © Georg Thieme Verlag KG Stuttgart · New York.

  14. A novel approach in the detoxification of intravenous buprenorphine dependence

    National Research Council Canada - National Science Library

    Sarkar, Sukanto; Subramaniam, Eswaran; Konthoujam, Janet

    2016-01-01

    .... We assessed the safety and efficacy of transdermal patch of buprenorphine with week long duration of action in the treatment of detoxification of IV buprenorphine dependence in view of its many advantages...

  15. Pharmacokinetics and pharmacodynamics of buprenorphine and sustained-release buprenorphine after administration to adult alpacas.

    Science.gov (United States)

    Dooley, S Bryce; Aarnes, Turi K; Lakritz, Jeffrey; Lerche, Phillip; Bednarski, Richard M; Hubbell, John A E

    2017-03-01

    OBJECTIVE To determine pharmacokinetics and pharmacodynamics of buprenorphine after IV and SC administration and of sustained-release (SR) buprenorphine after SC administration to adult alpacas. ANIMALS 6 alpacas. PROCEDURES Buprenorphine (0.02 mg/kg, IV and SC) and SR buprenorphine (0.12 mg/kg, SC) were administered to each alpaca, with a 14-day washout period between administrations. Twenty-one venous blood samples were collected over 96 hours and used to determine plasma concentrations of buprenorphine. Pharmacokinetic parameters were calculated by use of noncompartmental analysis. Pharmacodynamic parameters were assessed via sedation, heart and respiratory rates, and thermal and mechanical antinociception indices. RESULTS Mean ± SD maximum concentration after IV and SC administration of buprenorphine were 11.60 ± 4.50 ng/mL and 1.95 ± 0.80 ng/mL, respectively. Mean clearance was 3.00 ± 0.33 L/h/kg, and steady-state volume of distribution after IV administration was 3.8 ± l.0 L/kg. Terminal elimination half-life was 1.0 ± 0.2 hours and 2.7 ± 2.8 hours after IV and SC administration, respectively. Mean residence time was 1.3 ± 0.3 hours and 3.6 ± 3.7 hours after IV and SC administration, respectively. Bioavailability was 64 ± 28%. Plasma concentrations after SC administration of SR buprenorphine were below the LLOQ in samples from 4 alpacas. There were no significant changes in pharmacodynamic parameters after buprenorphine administration. Alpacas exhibited mild behavioral changes after all treatments. CONCLUSIONS AND CLINICAL RELEVANCE Buprenorphine administration to healthy alpacas resulted in moderate bioavailability, rapid clearance, and a short half-life. Plasma concentrations were detectable in only 2 alpacas after SC administration of SR buprenorphine.

  16. Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active

    Science.gov (United States)

    Brown, Sarah M.; Holtzman, Michael; Kim, Thomas; Kharasch, Evan D.

    2012-01-01

    Background The long-lasting high affinity opioid buprenorphine has complex pharmacology including ceiling effects with respect to analgesia and respiratory depression. Plasma concentrations of the major buprenorphine metabolites norbuprenorphine, buprenorphine-3-glucuronide, and norbuprenorphine-3-glucuronide approximate or exceed those of the parent drug. Buprenorphine glucuronide metabolites pharmacology is undefined. This investigation determined binding and pharmacological activity of the two glucuronide metabolites, and in comparison with buprenorphine and norbuprenorphine. Methods Competitive inhibition of radioligand binding to human mu, kappa, delta opioid and nociceptin receptors was used to determine glucuronide binding affinities for these receptors. Common opiate effects were assessed in vivo in Swiss Webster mice. Antinociception was assessed using a tail-flick assay, respiratory effects were measured using unrestrained whole-body plethysmography, and sedation was assessed by inhibition of locomotion measured by open-field testing. Results Buprenorphine-3-glucuronide had high affinity for human mu (Ki = 4.9±2.7 pM), delta (Ki = 270±0.4 nM), and nociceptin (Ki = 36±0.3 μM) but not kappa receptors. Norbuprenorphine-3-glucuronide had affinity for human kappa (Ki = 300±0.5 nM) and nociceptin (Ki= 18±0.2 μM) but not mu or delta receptors. At the dose tested, buprenorphine-3-glucuronide had a small antinociceptive effect. Neither glucuronide had significant effects on respiratory rate, but norbuprenorphine-3-glucuronide decreased tidal volume. Norbuprenorphine-3-glucuronide also caused sedation. Conclusions Both glucuronide metabolites of buprenorphine are biologically active at doses relevant to metabolite exposures which occur after buprenorphine. Activity of the glucuronides may contribute to the overall pharmacology of buprenorphine. PMID:22037640

  17. Maternal buprenorphine treatment and fetal neurobehavioral development.

    Science.gov (United States)

    Jansson, Lauren M; Velez, Martha; McConnell, Krystle; Spencer, Nancy; Tuten, Michelle; Jones, Hendree E; King, Van L; Gandotra, Neeraj; Milio, Lorraine A; Voegtline, Kristin; DiPietro, Janet A

    2017-05-01

    Gestational opioid use/misuse is escalating in the United States; however, little is understood about the fetal effects of medications used to treat maternal opioid use disorders. The purpose of this study was to determine the effect of maternal buprenorphine administration on longitudinal fetal neurobehavioral development. Forty-nine buprenorphine-maintained women who attended a substance use disorder treatment facility with generally uncomplicated pregnancies underwent fetal monitoring for 60 minutes at times of trough and peak maternal buprenorphine levels. Data were collected at 24, 28, 32, and 36 weeks gestation. Fetal neurobehavioral indicators (ie, heart rate, motor activity, and their integration [fetal movement-fetal heart rate coupling]) were collected via an actocardiograph, digitized and quantified. Longitudinal data analysis relied on hierarchic linear modeling. Fetal heart rate, heart rate variability, and heart rate accelerations were significantly reduced at peak vs trough maternal buprenorphine levels. Effects were significant either by or after 28 weeks gestation and tended to intensify with advancing gestation. Fetal motor activity and fetal movement-fetal heart rate coupling were depressed from peak to trough at 36 weeks gestation. Polysubstance exposure did not significantly affect fetal neurobehavioral parameters, with the exception that fetuses of heavier smokers moved significantly less than those of lighter smokers at 36 weeks gestation. By the end of gestation, higher maternal buprenorphine dose was related to depression of baseline fetal cardiac measures at trough. Maternal buprenorphine administration has acute suppressive effects on fetal heart rate and movement, and the magnitude of these effects increases as gestation progresses. Higher dose (≥13 mg) appears to exert greater depressive effects on measures of fetal heart rate and variability. These findings should be balanced against comparisons to gestational methadone effects

  18. Buprenorphine and Buprenorphine/Naloxone Diversion, Misuse, and Illicit Use: An International Review

    Science.gov (United States)

    Yokell, Michael A.; Zaller, Nickolas D.; Green, Traci C.; Rich, Josiah D.

    2011-01-01

    The diversion, misuse, and non-medically supervised use of buprenorphine and buprenorphine/naloxone by opioid users are reviewed. Buprenorphine and buprenorphine/naloxone are used globally as opioid analgesics and in the treatment of opioid dependency. Diversion of buprenorphine and buprenorphine/naloxone represents a complex medical and social issue, and has been widely documented in various geographical regions throughout the world. We first discuss the clinical properties of buprenorphine and its abuse potential. Second, we discuss its diversion and illicit use on an international level, as well as motivations for those activities. Third, we examine the medical risks and benefits of buprenorphine’s non-medically supervised use and misuse. These risks and benefits include the effect of buprenorphine’s use on HIV risk and the risk of its concomitant use with other medications and drugs of abuse. Finally, we discuss the implications of diversion, misuse, and non-medically supervised use (including potential measures to address issues of diversion); and potential areas for further research. PMID:21466501

  19. Epidural Naloxone to Prevent Buprenorphine Induced PONV

    Directory of Open Access Journals (Sweden)

    Ashok Jadon

    2008-01-01

    Full Text Available Epidural infusion of local analgesic and opioid are commonly used for postoperative pain relief. This combina-tion gives excellent anlgesia but nausea and vomiting remains a major concern. Low dose epidural naloxone prevents PONV induced by spinal opioids like morphine, fentanyl and sufentanil. However, it is not known that epidural naloxone administration prevents PONV induced by epidural buprenorphine. We have reported three cases of major abdominal operation in which lowdose epidural infusion of naloxone releived the symptom of buprenorphine induced severe PONV and improved the quality of analgesia.

  20. Implementing buprenorphine treatment in community settings in Australia: experiences from the Buprenorphine Implementation Trial.

    Science.gov (United States)

    Lintzeris, Nicholas; Ritter, Alison; Panjari, Mary; Clark, Nicolas; Kutin, Jozica; Bammer, Gabriele

    2004-01-01

    Buprenorphine was registered in Australia as a maintenance and detoxification agent for the management of opioid dependence in November, 2000, and became widely available in August, 2001. This paper provides an overview of key developments in the introduction of buprenorphine treatment in Australia, with an emphasis upon the delivery of services in community-based (primary care) settings. A central study in this work was the Buprenorphine Implementation Trial (BIT), a randomized, controlled trial comparing buprenorphine and methadone maintenance treatment delivered under naturalistic conditions by specialist and community-based service providers (general practitioners and community pharmacists) in 139 subjects across nineteen treatment sites. In addition to conventional patient outcome measures (treatment retention, drug use, psychosocial functioning, and cost effectiveness), the BIT study also involved the development and evaluation of clinical guidelines, training programs for clinicians, and client literature, which are described here. Integration of treatment systems (methadone with buprenorphine, specialist and primary-care programs) and factors thought to be important in the uptake of buprenorphine treatment in Australia since registration are discussed.

  1. Postcastration analgesia in ponies using buprenorphine hydrochloride.

    Science.gov (United States)

    Love, E J; Taylor, P M; Whay, H R; Murrell, J

    2013-06-15

    Buprenorphine has recently obtained UK Marketing Authorisation for horses. The analgesic effects are long lasting, and have considerable potential for postoperative pain relief. This observer blinded, randomised study aimed to evaluate postsurgical analgesia in ponies premedicated with buprenorphine prior to castration under intravenous anaesthesia. Ponies received either 0.01 mg/kg bodyweight (BW) buprenorphine (group B) or an equivalent volume of 5 per cent glucose (group C) given intravenously before induction of anaesthesia. Pain was assessed and recorded using dynamic interactive visual analogue scores (DIVAS 0-100) and a Simple Descriptive Scale (SDS 0-3) (high scores=most pain) before and 1, 3, 6, 9, 12 and 24 hours after anaesthesia. Rescue analgesia was given if DIVAS>40 mm. Data were analysed using the Mann-Whitney U test at PBuprenorphine did not produce any serious adverse effects. Buprenorphine at 0.01 mg/kg BW intravenously administered before anaesthesia provided near-comprehensive postoperative analgesia after surgical castration in ponies.

  2. Evaluation of tribromoethanol, tribromoethanol-buprenorphine and ...

    African Journals Online (AJOL)

    Effect of premedication with buprenorphine (BP) on efficacy and safety of tribromoethanol (TBE) - induced anaesthesia was evaluated and compared with anaesthesia induced by ketamine (K) and xylazine (X) combination in rats undergoing ovariectomy. Fifteen Sprague -Dawley rats (mean weight 246.5 ± 13.1g) were ...

  3. Evaluation of tribromoethanol, tribromoethanol-buprenorphine and ...

    African Journals Online (AJOL)

    olayemitoyin

    Thus care should be exercised when premedicating rats with buprenorphine prior to tribromoethanol admini- stration. Thermoregulation and periodic evaluation of temperature in surgical patient is an important aspect of monitoring during anaesthesia. This is so because surgical patient under general anaesthesia can lose.

  4. The Effect of Buprenorphine on Methamphetamine Cravings.

    Science.gov (United States)

    Salehi, Mehrdad; Emadossadat, Alireza; Kheirabadi, Gholam Reza; Maracy, Mohammad Reza; Sharbafchi, Mohammad Reza

    2015-12-01

    Methamphetamine (METH) abuse and dependence present a major global problem. We investigated the efficacy of adding buprenorphine in reducing METH cravings during treatment with the Matrix program. This was a randomized, double-blind, controlled clinical trial of 40 men between the age of 18 and 40 years who were referred to the addiction treatment center at Noor Hospital from December 2012 to September 2013. All of the selected subjects participated in the Matrix program and were randomly assigned into 2 groups and given either buprenorphine or a placebo. A 4-month intervention program with buprenorphine or a placebo was arranged for each group. Demographic variables of the 2 groups, descriptive indices from the cocaine craving questionnaire-brief (CCQ-Brief), the ratio of urine tests positive for METH, and the frequency of drug complications were regularly evaluated in both groups every 2 weeks and, if not possible, by the third or fourth week. All analyses were performed by SPSS20 using analysis of covariance, χ, and t tests. The average of indices from the cocaine craving questionnaire-brief score, except the 2 initial measurements, was significantly lower in the intervention group in all measurements (P < 0.05). Apart from weeks 3 and 28, the ratio of positive tests was significantly different in all measurements in both groups (P < 0.05). Buprenorphine augmentation, in comparison with the placebo, significantly reduced the craving to use METH during treatment with the Matrix program.

  5. A comparison of acepromazine-buprenorphine and medetomidine-buprenorphine for preanesthetic medication of dogs.

    Science.gov (United States)

    Grint, Nicola J; Alderson, Briony; Dugdale, Alexandra H A

    2010-12-15

    To assess sedative and cardiopulmonary effects of premedication with a medetomidine-buprenorphine or acepromazine-buprenorphine combination in dogs anesthetized with propofol and isoflurane. Randomized controlled clinical trial. 90 dogs undergoing routine surgical and diagnostic procedures. Dogs were randomly assigned to 1 of 3 premedication groups: group 1 (acepromazine, 0.03 mg/kg [0.014 mg/lb], IM; buprenorphine, 0.02 mg/kg [0.009 mg/lb], IM), 2 (medetomidine, 5 μg/kg [2.3 μg/lb], IM; buprenorphine, 0.02 mg/kg, IM), or 3 (medetomidine, 10 μg/kg [4.5 μg/lb], IM; buprenorphine, 0.02 mg/kg, IM). Anesthesia was induced with propofol and maintained with isoflurane in oxygen. Simple descriptive scores for sedation were assigned 15 minutes (groups 2 and 3) and 30 minutes (group 1) after premedication administration. Basic cardiopulmonary data were recorded throughout the anesthetic period. Times to recovery from anesthesia were recorded. Sedation scores did not differ significantly among groups. Mean and diastolic blood pressures were significantly lower and heart rate was significantly higher in group 1 than in the other groups. Mean end-tidal partial pressure of CO(2) was significantly lower and respiratory rate was significantly higher in group 1 than in the other groups. There were no significant differences in anesthetic recovery times between groups. Results suggested that either acepromazine or medetomidine could be used in combination with buprenorphine for premedication of dogs anesthetized with propofol and isoflurane for routine surgical and diagnostic procedures. Arterial blood pressure was better maintained with the medetomidine-buprenorphine combinations, but tissue perfusion was not investigated.

  6. Quantitation of Buprenorphine, Norbuprenorphine, Buprenorphine Glucuronide, Norbuprenorphine Glucuronide, and Naloxone in Urine by LC-MS/MS.

    Science.gov (United States)

    Marin, Stephanie J; McMillin, Gwendolyn A

    2016-01-01

    Buprenorphine is an opioid drug that has been used to treat opioid dependence on an outpatient basis, and is also prescribed for managing moderate to severe pain. Some formulations of buprenorphine also contain naloxone to discourage misuse. The major metabolite of buprenorphine is norbuprenorphine. Both compounds are pharmacologically active and both are extensively metabolized to their glucuronide conjugates, which are also active metabolites. Direct quantitation of the glucuronide conjugates in conjunction with free buprenorphine, norbuprenorphine, and naloxone in urine can distinguish compliance with prescribed therapy from specimen adulteration intended to mimic compliance with prescribed buprenorphine. This chapter quantitates buprenorphine, norbuprenorphine, their glucuronide conjugates and naloxone directly in urine by liquid chromatography tandem mass spectrometry (LC-MS/MS). Urine is pretreated with formic acid and undergoes solid phase extraction (SPE) prior to analysis by LC-MS/MS.

  7. Buprenorphine infrequently found in fatal overdose in New York City.

    Science.gov (United States)

    Paone, Denise; Tuazon, Ellenie; Stajic, Marina; Sampson, Barbara; Allen, Bennett; Mantha, Shivani; Kunins, Hillary

    2015-10-01

    Buprenorphine is an opioid agonist medication that is both safe and effective in the treatment of opioid use disorders and the prevention of opioid overdoses. Despite this, media coverage has highlighted public concerns about the potential safety consequences of buprenorphine misuse and diversion. To address the possible contribution of buprenorphine to overdose mortality, we systematically tested post mortem blood specimens from decedents who had died of an unintentional drug overdoses in 2013. We retrospectively tested consecutive drug overdose cases that occurred from June through October 2013. Cases with available blood specimens were tested for buprenorphine and norbuprenorphine using liquid chromatography-tandem mass spectrometry. Toxicology results were linked to death certificates and case files from New York City Vital Statistics and New York City Office of the Chief Medical Examiner. Of the 98 unintentional drug overdose fatalities tested, only 2 (2.0%) tested positive for buprenorphine metabolites. All 98 unintentional fatalities involved multiple substances. Buprenorphine was infrequently found in drug overdose deaths in New York City. Since the safety and efficacy of buprenorphine are well documented, and overdoses resulting from buprenorphine treatment or diversion are very rare, facilitating access to buprenorphine treatment is strongly recommended. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Opiate withdrawal syndrome in buprenorphine abusers admitted to ...

    African Journals Online (AJOL)

    Background: Illicit use of high dosage buprenorphine has been well documented in several countries, including Tunisia. Objectives: The aim of this survey is to assess the buprenorphine withdrawal syndrome time course, and how it may be affected by the population characteristics among subjects admitted to a ...

  9. Respiratory and cardiovascular effects of buprenorphine in conscious rabbits.

    Science.gov (United States)

    Shafford, Heidi L; Schadt, James C

    2008-07-01

    To quantify the respiratory and cardiovascular effects of intravenous or subcutaneous buprenorphine in conscious rabbits. Prospective experimental trial. Eight healthy, young adult New Zealand white rabbits (four female). Rabbits were instrumented with intraabdominal arterial and venous catheters and diaphragmatic electromyographic electrodes 2 weeks before experiments. Arterial blood pressure, arterial blood gases, heart rate and respiratory rate were monitored during experiments. Buprenorphine (0.06 mg) was administered either intravenously or subcutaneously to conscious rabbits. Respiratory and cardiovascular parameters were compared to baseline at 10 and 22 minutes after intravenous buprenorphine administration, and at 30, 60, and 90 minutes after subcutaneous buprenorphine administration. Buprenorphine administration, at a dose of approximately 0.02 mg kg(-1), did not change blood pressure or heart rate. However, respiratory rate decreased from 252 +/- 26 to 39 +/- 26 breaths minute(-1) (mean +/- SD), and from 306 +/- 38 to 90 +/- 38 breaths minute(-1) following intravenous and subcutaneous administration of buprenorphine, respectively. Subsequent to intravenous and subcutaneous buprenorphine, arterial oxygen tension decreased from 88 +/- 4 to 72 +/- 4 mmHg (11.7 +/- 0.5 to 9.6 +/- 0.5 kPa) and from 87 +/- 3 to 77 +/- 3 mmHg (11.6 +/- 0.4 to 10.3 +/- 0.4 kPa), respectively. Buprenorphine, by either route of administration, increased arterial carbon dioxide tension from 36 to 41 mmHg (4.8-5.5 kPa) and increased the alveolar-arterial oxygen gradient from 15 to > or =20 mmHg (2 to > or =2.7 kPa). Buprenorphine administration decreased respiratory rate and produced mild hypoxemia in conscious rabbits. While these changes were well tolerated by healthy animals, caution should be exercised when administering buprenorphine to rabbits predisposed to respiratory depression.

  10. BUPRENORPHINE DECREASES THE CCL2-MEDIATED CHEMOTACTIC RESPONSE OF MONOCYTES

    Science.gov (United States)

    Carvallo, Loreto; Lopez, Lillie; Che, Fa-Yun; Lim, Jihyeon; Eugenin, Eliseo; Williams, Dionna W.; Nieves, Edward; Calderon, Tina M.; Madrid-Aliste, Carlos; Fiser, Andras; Weiss, Louis; Angeletti, Ruth Hogue; Berman, Joan W.

    2015-01-01

    Despite successful cART, approximately 60% of HIV infected people exhibit HIV associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9, were identified and had not been shown previously be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction. PMID:25716997

  11. A Comparison of Buprenorphine + Naloxone to Buprenorphine and Methadone in the Treatment of Opioid Dependence during Pregnancy: Maternal and Neonatal Outcomes

    Directory of Open Access Journals (Sweden)

    Ingunn O. Lund

    2013-01-01

    Full Text Available Given that buprenorphine + naloxone is prescribed for opioid-dependent pregnant women, it is important to examine the extent to which it differs from buprenorphine alone, methadone, or methadone-assisted withdrawal on neonatal and maternal outcomes. Summary statistics on maternal and neonatal outcomes were collected from 7 previously published studies examining treatment for opioid-dependent pregnant women that represented a range of research methodologies. Outcomes from these studies were compared to the same outcomes for 10 women treated with the combined buprenorphine + naloxone product. There were no significant differences in maternal outcomes for buprenorphine + naloxone compared to buprenorphine, methadone, or methadone-assisted withdrawal. Preliminary findings suggest no significant adverse maternal or neonatal outcomes related to the use of buprenorphine + naloxone for the treatment of opioid dependence during pregnancy. However, further research should examine possible differences between buprenorphine + naloxone and buprenorphine alone or methadone in fetal physical development.

  12. Buprenorphine prescribing practice trends and attitudes among New York providers.

    Science.gov (United States)

    Kermack, Andrea; Flannery, Mara; Tofighi, Babak; McNeely, Jennifer; Lee, Joshua D

    2017-03-01

    Buprenorphine office-based opioid maintenance is an increasingly common form of treatment for opioid use disorders. However, total prescribing has not kept pace with the current opioid and overdose epidemic and access remains scarce among the underserved. This study sought to assess current provider attitudes and clinical practices among a targeted sample of primarily New York City public sector buprenorphine prescribers. A cross-sectional online survey purposefully sampled buprenorphine prescribers in NYC with a focus on those serving Medicaid and uninsured patient populations. Expert review of local provider networks, snowball referrals, and in-person networking generated an email list, which received a survey link. A brief 25-question instrument queried provider and practice demographics, prescribing practices including induction approaches and attitudes regarding common hot topics (e.g., buprenorphine diversion, prescriber patient limits, insurance issues, ancillary treatments). Of 132 email invitations, N=72 respondents completed (n=64) or partially completed (n=8) the survey between January and April 2016. Most (79%) were Medicaid providers in non-psychiatric specialties (72%), working in a hospital-based or community general practice (51%), and board-certified in addiction medicine or psychiatry (58%). Practice sizes were generally 100 patients or fewer (71%); many providers (64%) individually prescribed buprenorphine Buprenorphine diversion was not rated as an important practice barrier. In conclusion, this targeted survey of buprenorphine prescribers in NYC treating primarily underserved populations showed a consistent pattern of part-time prescribing to modest volumes of patients, routine use of unobserved buprenorphine induction, and primarily elective referrals to psychosocial counseling. Barriers to prescribing included prior authorization requirements, lack of clinical resources (space, staff) and psychiatric services. Federal and local efforts to

  13. Buprenorphine and Opioid Antagonism, Tolerance, and Naltrexone-Precipitated Withdrawal

    Science.gov (United States)

    Bergman, Jack

    2011-01-01

    The dual antagonist effects of the mixed-action μ-opioid partial agonist/κ-opioid antagonist buprenorphine have not been previously compared in behavioral studies, and it is unknown whether they are comparably modified by chronic exposure. To address this question, the dose-related effects of levorphanol, trans-(−)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide (U50,488), heroin, and naltrexone on food-maintained behavior in rhesus monkeys were studied after acute and chronic treatment with buprenorphine (0.3 mg/kg/day). In acute studies, the effects of levorphanol and U50,488 were determined at differing times after buprenorphine (0.003–10.0 mg/kg i.m.). Results show that buprenorphine produced similar, dose-dependent rightward shifts of the levorphanol and U50,488 dose-response curves that persisted for ≥24 h after doses larger than 0.1 mg/kg buprenorphine. During chronic treatment with buprenorphine, the effects of levorphanol, U50,488, heroin, and naltrexone were similarly determined at differing times (10 min to 48 h) after intramuscular injection. Overall, results show that buprenorphine produced comparable 3- to 10-fold rightward shifts in the U50,488 dose-response curve under both acute and chronic conditions, but that chronic buprenorphine produced larger (10- to ≥30-fold) rightward shifts in the heroin dose-effect function than observed acutely. Naltrexone decreased operant responding in buprenorphine-treated monkeys, and the position of the naltrexone dose-effect curve shifted increasingly to the left as the time after daily buprenorphine treatment increased from 10 min to 48 h. These results suggest that the μ-antagonist, but not the κ-antagonist, effects of buprenorphine are augmented during chronic treatment. In addition, the leftward shift of the naltrexone dose-effect function suggests that daily administration of 0.3 mg/kg buprenorphine is adequate to produce opioid dependence. PMID:21051498

  14. Predictive factors for relapse in patients on buprenorphine maintenance.

    Science.gov (United States)

    Ferri, Michael; Finlayson, Alistair J Reid; Wang, Li; Martin, Peter R

    2014-01-01

    Despite the dramatic increase in the use of buprenorphine for the treatment of opioid dependence, clinical outcomes of this treatment approach continue to need evaluation. This study examines factors associated with relapse and retention during buprenorphine treatment in a sample of opioid dependent outpatients. In a retrospective chart review of 62 patients with opioid dependence, relapse was determined by self-report, urine toxicology screens, and by checking the state controlled substance monitoring database. Data was analyzed using two-way tests of association and logistic regression. Patients with comorbid anxiety disorders, active benzodiazepine use (contrary to clinic policy), or active alcohol abuse, were significantly more likely to relapse. Patients who relapsed were also more likely to be on a higher buprenorphine maintenance dose. This study identifies relapse risk factors during buprenorphine treatment for opioid dependence. Future research is needed to determine whether modifying these factors may lead to improved treatment outcomes. © American Academy of Addiction Psychiatry.

  15. Pharmacokinetic-pharmacodynamic modelling of intravenous buprenorphine in conscious horses.

    Science.gov (United States)

    Love, Emma J; Pelligand, Ludovic; Taylor, Polly M; Murrell, Joanna C; Sear, John W

    2015-01-01

    Describe the pharmacokinetics of buprenorphine and norbuprenorphine in horses and to relate the plasma buprenorphine concentration to the pharmacodynamic effects. Single phase non-blinded study. Six dedicated research horses, aged 3-10 years and weighing 480-515 kg. Thermal and mechanical nociceptive thresholds, heart and respiratory rates and locomotor activity were measured before and 15, 30, 45 & 60 minutes and 2, 4, 6, 8, 12 & 24 hours post-administration of 10 μg kg(-1) buprenorphine IV. Intestinal motility was measured 1, 6, 12 & 24 hours after buprenorphine administration. Venous blood samples were obtained before administration of buprenorphine 10 μg kg(-1) IV and 1, 2, 4, 6, 10, 15, 30, 45 & 60 minutes, and 2, 4, 6, 8, 12 & 24 hours afterwards. Plasma buprenorphine and norbuprenorphine concentrations were measured using a liquid chromatography-tandem mass spectroscopy (LC-MS/MS) assay with solid-phase extraction. A non-compartmental method was used for analysis of the plasma concentration-time data and plasma buprenorphine concentrations were modelled against two dynamic effects (change in thermal threshold and mechanical threshold) using a simple Emax model. Plasma buprenorphine concentrations were detectable to 480 minutes in all horses and to 720 minutes in two out of six horses. Norbuprenorphine was not detected. Thermal thresholds increased from 15 minutes post-buprenorphine administration until the 8-12 hour time points. The increase in mechanical threshold ranged from 3.5 to 6.0 Newtons (median: 4.4 N); and was associated with plasma buprenorphine concentrations in the range 0.34-2.45 ng mL(-1) . The suitability of the use of buprenorphine for peri-operative analgesia in the horse is supported by the present study. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  16. Factors associated with buprenorphine versus methadone use in pregnancy.

    Science.gov (United States)

    Krans, Elizabeth E; Bogen, Debra; Richardson, Gale; Park, Seo Young; Dunn, Shannon L; Day, Nancy

    2016-01-01

    Buprenorphine has recently emerged as a safe and effective treatment option for pregnant women with opioid use disorder (OUD) and is associated with superior neonatal outcomes. This study characterized and compared patient populations who used buprenorphine versus methadone during pregnancy in an academic medical center. Observational retrospective cohort evaluation of 791 pregnant women with OUD on opioid maintenance treatment from 2009 to 2012. Buprenorphine versus methadone use was defined as use after either (a) conversion from illicit opioid use during pregnancy or (b) ongoing prepregnancy use. Multivariable logistic regression was used to identify patient characteristics predictive of buprenorphine use. Among 791 pregnant women, 608 (76.9%) used methadone and 183 (23.1%) used buprenorphine. From 2009 to 2012, buprenorphine use during pregnancy increased from 10.1% to 33.2%. Pregnant women using buprenorphine were significantly more likely to be older, married, employed, have more education, and have a history of prescription opioid use compared with women using methadone. In contrast, pregnant women using methadone were significantly more likely to have hepatitis C virus infection, use cocaine, benzodiazepines, or marijuana, and have a history of heroin and/or intravenous opioid use. In multivariable analysis, pregnant women who were older (odds ratio [OR] = 1.01; 95% confidence interval [CI]: 1.02, 1.11), were employed (1.87; 1.20, 2.90), and had a history of opioid maintenance treatment prior to pregnancy (2.68; 1.78, 4.02) were more likely to use buprenorphine during pregnancy. Pregnant women with a history of benzodiazepine use (0.48; 0.30, 0.77), who had children no longer in their legal custody (0.63; 0.40, 0.99), and who had a partner with a substance use history (0.37; 0.22, 0.63) were less likely to use buprenorphine during pregnancy. Disparities exist among patients who use buprenorphine versus methadone during pregnancy and indicate the need to

  17. I Heard About It From a Friend: Assessing Interest in Buprenorphine Treatment

    Science.gov (United States)

    Fox, Aaron D.; Shah, Pooja A.; Sohler, Nancy L.; Lopez, Carolina M.; Starrels, Joanna L.; Cunningham, Chinazo O.

    2013-01-01

    Background In the United States, opioid abuse and dependence continue to be a growing problem, while treatment for opioid abuse and dependence remains fairly static. Buprenorphine treatment for opioid dependence is safe and effective but underutilized. Prior research has demonstrated low awareness and use of buprenorphine among marginalized groups. This study investigates syringe exchange participants’ awareness of, exposure to, and interest in buprenorphine treatment. Methods Syringe exchange participants were recruited from a mobile unit performing outreach to nine street-side sites in New York City. Computer-based interviews were conducted to determine: (1) opioid users’ awareness of, exposure to, and interest in buprenorphine treatment; and (2) the association between awareness or exposure and interest in buprenorphine treatment. Logistic regression models were used to examine the associations between awareness, direct exposure (i.e. having taken buprenorphine), or indirect exposure (i.e. knowing someone who had taken buprenorphine) and interest in buprenorphine treatment. Results Of 158 opioid users, 70% were aware of, 32% had direct exposure to, and 31% had indirect exposure to buprenorphine; 12% had been prescribed buprenorphine. Of 138 opioid users who had never been prescribed buprenorphine, 57% were interested in buprenorphine treatment. In multivariate models, indirect exposure was associated with interest in buprenorphine treatment (AOR = 2.65, 95% CI: 1.22 – 5.77), but awareness and direct exposure were not. Conclusions Syringe exchange participants were mostly aware of buprenorphine and interested in treatment, but few had actually been prescribed buprenorphine. Because indirect exposure to buprenorphine was associated with interest in treatment, future interventions could capitalize on indirect exposure, such as through peer mentorship, to address underutilization of buprenorphine treatment. PMID:24588297

  18. A review of the studies using buprenorphine in cats.

    Science.gov (United States)

    Steagall, P V M; Monteiro-Steagall, B P; Taylor, P M

    2014-01-01

    Pain management is a crucial component of feline medicine and surgery. This review critically evaluates studies using buprenorphine in cats and highlights the clinical application of the opioid in this species. The pharmacokinetic-pharmacodynamic (PK-PD) modeling of IV buprenorphine has been best described by a combined effect compartmental/receptor association-dissociation model with negative hysteresis. Therefore, plasma concentrations of the drug are not correlated with analgesia, and clinicians should not expect to observe pain relief immediately after drug administration. In addition, a ceiling effect has not been demonstrated after administration of clinical doses of buprenorphine in cats; dosages of up to 0.04 mg/kg have been reported. The route of administration influences the onset, duration, and magnitude of antinociception and analgesia when using this drug in cats. At clinical dosages, the SC route of administration does not appear to provide adequate antinociception and analgesia whereas the buccal route has produced inconsistent results. Intravenous or IM administration at a dosage of 0.02-0.04 mg/kg is the preferred for treatment of pain in the acute setting. A literature search found 14 clinical trials evaluating buprenorphine sedation, analgesia, or both in cats. There were 22 original research studies reporting the antinociceptive effects of buprenorphine by means of thermal threshold, mechanical threshold, or both, minimal alveolar concentration, or PK-PD. Individual variability in response to buprenorphine administration has been reported, indicating that buprenorphine may not provide sufficient analgesia in some cats. Pain assessment is important when evaluating the efficacy of buprenorphine and determining whether additional analgesic treatment is needed. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  19. A Review of the Studies Using Buprenorphine in Cats

    OpenAIRE

    Steagall, P.V.M.; Monteiro?Steagall, B.P.; Taylor, P.M.

    2014-01-01

    Pain management is a crucial component of feline medicine and surgery. This review critically evaluates studies using buprenorphine in cats and highlights the clinical application of the opioid in this species. The pharmacokinetic?pharmacodynamic (PK?PD) modeling of IV buprenorphine has been best described by a combined effect compartmental/receptor association?dissociation model with negative hysteresis. Therefore, plasma concentrations of the drug are not correlated with analgesia, and clin...

  20. Buprenorphine Versus Methadone for Opioid Dependence in Pregnancy.

    Science.gov (United States)

    Noormohammadi, Arezo; Forinash, Alicia; Yancey, Abigail; Crannage, Erica; Campbell, Kristin; Shyken, Jaye

    2016-08-01

    To evaluate maternal and neonatal safety outcomes for methadone and buprenorphine in the obstetric population. A literature search of PubMed (1966 to March 2016) and EMBASE (1973 to March 2016) was completed using the search terms buprenorphine, methadone, pregnancy, opioid, and neonatal abstinence syndrome Priority was given to randomized controlled trials and trials directly comparing buprenorphine and methadone during pregnancy. The bibliographies were reviewed for other relevant articles. All human studies published in English, that compared methadone and buprenorphine use in pregnancy were evaluated. Because of the limited number of obstetric studies, only 5 critical studies were found. Buprenorphine significantly improved or had similar outcomes to methadone for development of neonatal abstinence syndrome (NAS), percentage of infants requiring treatment for NAS (20%-47% vs 45.5%-57%, respectively), total amount of morphine used to treat NAS (0.472-3.4 vs 1.862-10.4 mg, respectively), duration of NAS (4.1-5.6 vs 5.3-9.9 days, respectively), peak NAS (3.9-11 vs 4.9-12.8 score, respectively), infant hospital stay (6.8-10.6 vs 8.1-17.5 days, respectively), and gestational age at delivery (38.8-39.7 vs 37.9-38.8 weeks, respectively). No difference was found with other neonatal or maternal outcomes. Both methadone and buprenorphine are effective agents, with improved safety compared with continued nonmedical opioid use during pregnancy. There is evidence to suggest that buprenorphine should be considered as an equivalent option to methadone for use in pregnancy; however, larger studies are still needed to fully evaluate buprenorphine safety and advantages over methadone in the obstetric population. © The Author(s) 2016.

  1. Buprenorphine in combination with naloxone at a ratio of 15:1 does not enhance antinociception from buprenorphine in healthy cats.

    Science.gov (United States)

    Slingsby, L S; Murrell, J C; Taylor, P M

    2012-06-01

    Naloxone can enhance the antinociceptive/analgesic effects of buprenorphine in humans and rats. The antinociceptive effects of a patented 15:1 buprenorphine:naloxone combination was investigated in cats using a thermal and mechanical nociceptive model. Twelve cats received buprenorphine 10 μg/kg, naloxone 0.67 μg/kg or a buprenorphine-naloxone combination intramuscularly in a randomised cross over study. Using thermal and mechanical analgesiometry validated in the cat, pre-treatment baselines were measured. Following test drug administration, thresholds were studied for the next 24h. Naloxone did not enhance the thermal antinociceptive effect of buprenorphine. The results from this study are in agreement with previously published work showing that naloxone antagonises the effects of clinically analgesic doses of buprenorphine. Mechanical nociceptive thresholds were not affected by buprenorphine. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Buprenorphine dosing choices in specific populations: review of expert opinion.

    Science.gov (United States)

    Maremmani, Icro; Rolland, Benjamin; Somaini, Lorenzo; Roncero, Carlos; Reimer, Jens; Wright, Nat; Littlewood, Richard; Krajci, Peter; Alho, Hannu; D'Agnone, Oscar; Simon, Nicolas

    2016-09-01

    Treatment of opioid dependence with buprenorphine improves outcomes. Typical dosing ranges for all patients from clinical evidence and as defined in the product information are wide. For specific groups with complex clinical scenarios, there is no clear consensus on dosing choices to achieve best possible outcomes. The doses of buprenorphine used in 6 European countries was reviewed. A review of published evidence supported rapid induction with buprenorphine and the benefits of higher doses but did not identify clearly useful guidance on dosing choices for groups with complex clinical scenarios. An expert group of physicians with experience in addiction care participated in a discussion meeting to share clinical practice experience and develop a consensus on dosing choices. There was general agreement that treatment outcomes can be improved by optimising buprenorphine doses in specific subgroups. Specific groups in whom buprenorphine doses may be too low and who could have better outcomes with optimised dosing were identified on the basis of clinical practice experience. These groups include people with severe addiction, high tolerance to opioids, and psychiatric comorbidities. In these groups it is recommended to review dosing choices to ensure buprenorphine dosing is sufficient.

  3. Buprenorphine Initiation and Linkage to Outpatient Buprenorphine do not Reduce Frequency of Injection Opiate Use Following Hospitalization.

    Science.gov (United States)

    Cushman, Phoebe A; Liebschutz, Jane M; Anderson, Bradley J; Moreau, Merredith R; Stein, Michael D

    2016-09-01

    Buprenorphine has established effectiveness for outpatient treatment of opioid use disorder. Our previously published STOP (Suboxone Transition to Opiate Program) trial showed that buprenorphine induction, stabilization, and linkage to outpatient treatment in opioid-dependent inpatients (injection and non-injection drug users) decreased illicit opioid use over 6months. The present study was a planned subgroup analysis of injection opiate users from STOP. To determine if inpatient buprenorphine initiation and linkage to outpatient buprenorphine reduce injection opiate users' frequency of injection opiate use (IOU). Inpatient injection opiate users at a safety-net hospital were randomized to buprenorphine linkage (induction, stabilization, bridge prescription, and facilitated referral to outpatient treatment) or detoxification (5-day inpatient buprenorphine taper). Conditional fixed-effects Poisson regression was used to estimate the effects of intervention on 30-day (self-report) at 1, 3, and 6months, measured using 30-day timeline follow-back. The secondary outcome was linkage effectiveness, measured as % presenting to initial outpatient buprenorphine visits after hospital discharge. Analysis was limited to persons (n=62 randomized to detoxification and n=51 to linkage) with baseline IOU. There were no significant differences in age, ethnicity, or baseline IOU frequency. At follow-up, linkage patients (70.6%) were significantly more likely (pbuprenorphine visits than detoxification patients (9.7%). However, there was no significant between group difference in the rate of IOU at 1- (IRR=0.73, p=0.32), 3- (IRR=1.20, p=0.54), or 6-month (IRR=0.73, p=0.23) follow-ups. Using person-day analysis, participants self-reported IOU on 5.8% of follow-up days in which they used prescription buprenorphine and 37.5% of non-buprenorphine days. Using a generalized estimating equation, the estimated odds of IOU was 4.57 times higher (pbuprenorphine days. Despite STOP's success in

  4. Effect of Telaprevir on the Pharmacokinetics of Buprenorphine in Volunteers on Stable Buprenorphine/Naloxone Maintenance Therapy

    Science.gov (United States)

    Luo, Xia; Trevejo, Jose; van Heeswijk, Rolf P. G.; Smith, Frances

    2012-01-01

    This was an open-label, single-sequence trial in hepatitis C virus-negative volunteers on stable, individualized, buprenorphine maintenance therapy. Telaprevir at 750 mg every 8 h was coadministered with buprenorphine/naloxone (4:1 ratio as sublingual tablets) for 7 days with food. Pharmacokinetic profiles of buprenorphine, norbuprenorphine, and naloxone were measured over the 24-hour dosing interval on day −1 (buprenorphine/naloxone alone, reference) and day 7 of telaprevir coadministration (test). Geometric least-squares mean ratios and associated 90% confidence intervals of treatment ratios (test/reference) were calculated using log-transformed pharmacokinetic parameters. Opioid withdrawal symptoms were evaluated throughout the study (via questionnaires and pupillometry). Pharmacokinetic data were available for 14 and 13 volunteers on day −1 and day 7, respectively. The area under the concentration-time curve (AUC) for buprenorphine was unchanged and the maximum concentration of drug in serum (Cmax) for buprenorphine, Cmax and AUC for norbuprenorphine, and Cmax naxolone were modestly decreased during coadministration with telaprevir. Geometric least-squares mean ratios (90% confidence intervals) for buprenorphine were 0.80 (0.69, 0.93) for the Cmax and 0.96 (0.84, 1.10) for the AUC from 0 to 24 h (AUC0–24); for norbuprenorphine, values were 0.85 (0.66, 1.09) for Cmax and 0.91 (0.71, 1.16) for AUC0–24; for naloxone, the Cmax was 0.84 (0.62, 1.13). Coadministration of telaprevir did not increase withdrawal symptom frequency, and there were no serious adverse events reported during or after completion of telaprevir coadministration. Results suggest dose adjustment may not be necessary when telaprevir and buprenorphine/naloxone are coadministered. PMID:22564847

  5. Plasma concentrations of buprenorphine following a single subcutaneous administration of a sustained release formulation of buprenorphine in sheep.

    Science.gov (United States)

    Zullian, Chiara; Lema, Pablo; Lavoie, Melissa; Dodelet-Devillers, Aurore; Beaudry, Francis; Vachon, Pascal

    2016-07-01

    The goal of the present study was to evaluate the potential use of slow release buprenorphine in sheep. Twelve adult female sheep (6 Dorset and 6 Suffolk, 12 months of age) were used for this project and were divided into 2 experimental groups (n = 6/group comprising 3 Dorset and 3 Suffolk sheep). Sustained release (SR) buprenorphine was administered subcutaneously in the scapular region at a concentration of 0.1 mg/kg body weight (BW) for group 1 and of 0.05 mg/kg BW for group 2. Following blood collections at selected time points, plasma concentrations of buprenorphine was performed by tandem liquid chromatograph-mass spectrometry. Mean buprenorphine concentration was above 0.1 ng/mL at 48 h up to 192 h post-injection for group 1 and it was above 0.1 ng/mL at 48 h up to 72 h post-injection for group 2. In conclusion, a long lasting potential analgesic plasma level of buprenorphine is attained following a single subcutaneous injection of 0.1 mg/kg BW of SR buprenorphine in sheep. However the effective analgesic plasma threshold still needs to be determined in sheep.

  6. Population pharmacokinetics of buprenorphine following a two-stage intravenous infusion in healthy volunteers

    DEFF Research Database (Denmark)

    Jensen, Mette Lykke; Foster, David J.R.; Upton, Richard N.

    2007-01-01

    The aim of this investigation was to characterize the pharmacokinetics of buprenorphine following administration of an intravenous (i.v.) infusion. To date, the population kinetics of buprenorphine has been described for bolus administration only.......The aim of this investigation was to characterize the pharmacokinetics of buprenorphine following administration of an intravenous (i.v.) infusion. To date, the population kinetics of buprenorphine has been described for bolus administration only....

  7. The effect of voluntarily ingested buprenorphine on rats subjected to surgically induced global cerebral ischaemia

    DEFF Research Database (Denmark)

    Kalliokoski, Otto Henrik; Abelson, Klas; Koch, Janne

    2010-01-01

    The effect of perioperatively administered buprenorphine analgesia on rats subjected to surgically induced global ischaemia was assessed. Rats supplied with buprenorphine, mixed in nut paste for voluntary ingestion, displayed significant reductions in postoperative excretions of faecal...... in buprenorphine-treated and untreated animals. A part from a slightly higher hyperthermia immediately after surgery and typical opiate-associated behaviour, the buprenorphine treatment had no apparent adverse effects on the experimental model. In contrast, the analgesic treatment improved the model by minimizing...

  8. BUPRENORPHINE-NALXONE THERAPY IN PAIN MANAGEMENT

    Science.gov (United States)

    Chen, Kelly Yan; Chen, Lucy; Mao, Jianren

    2014-01-01

    Buprenorphine-naloxone (bup/nal in 4:1 ratio; Suboxone®, Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration for outpatient office-based addiction treatment. In the past few years, bup/nal has been increasingly prescribed off-label for chronic pain management. The current data suggests that bup/nal may provide pain relief in chronic pain patients with opioid dependence or addiction. However, the unique pharmacological profile of bup/nal confers it to be a weak analgesic that is unlikely to provide adequate pain relief for patients without opioid dependence or addiction. Possible mechanisms of pain relief by bup/nal therapy in opioid-dependent chronic pain patients may include reversal of opioid-induced hyperalgesia as well as improvement in opioid tolerance and addiction. Additional studies are needed to assess the implication of bup/nal therapy in clinical anesthesia and perioperative pain management. PMID:24509068

  9. 78 FR 34108 - Determination That SUBOXONE (Buprenorphine Hydrochloride and Naloxone Hydrochloride) Sublingual...

    Science.gov (United States)

    2013-06-06

    ... HUMAN SERVICES Food and Drug Administration Determination That SUBOXONE (Buprenorphine Hydrochloride and... (buprenorphine hydrochloride (HCl) and naloxone HCl) sublingual tablets, 2 milligrams (mg)/0.5 mg and 8 mg/2 mg... to approve abbreviated new drug applications (ANDAs) for buprenorphine HCl and naloxone HCl...

  10. Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial.

    Science.gov (United States)

    Rosenthal, Richard N; Lofwall, Michelle R; Kim, Sonnie; Chen, Michael; Beebe, Katherine L; Vocci, Frank J

    2016-07-19

    The effectiveness of buprenorphine treatment of opioid dependence is limited by suboptimal medication adherence, abuse, and diversion. To determine whether 6-month buprenorphine implants are noninferior to daily sublingual buprenorphine as maintenance treatment for opioid-dependent patients with stable abstinence. Outpatient, randomized, active-controlled, 24-week, double-blind, double-dummy study conducted at 21 US sites from June 26, 2014, through May 18, 2015. Outpatients were prescribed daily sublingual buprenorphine for 6 months or more, were abstinent while taking 8 mg/d or less of sublingual buprenorphine for 90 days or longer, and were determined to be clinically stable by their physician. Participants were randomized to receive sublingual buprenorphine plus 4 placebo implants or sublingual placebo plus four 80-mg buprenorphine hydrochloride implants (expected efficacy, 24 weeks). The primary end point was between-group difference in proportion of responders (≥4 of 6 months without opioid-positive urine test result [monthly and 4 times randomly] and self-report). The noninferiority established for the lower bound of the 95% confidence interval was greater than -0.20 (P buprenorphine with placebo implants and 87 to buprenorphine implants with sublingual placebo; 165 of 177 (93.2%) completed the trial. Eighty-one of 84 (96.4%) receiving buprenorphine implants and 78 of 89 (87.6%) receiving sublingual buprenorphine were responders, an 8.8% difference (1-sided 97.5% CI, 0.009 to ∞; P buprenorphine implants and 64 of 89 (71.9%) receiving sublingual buprenorphine maintained opioid abstinence (hazard ratio, 13.8; 95% CI, 0.018-0.258; P = .03). Non-implant-related and implant-related adverse events occurred in 48.3% and 23% of the buprenorphine implant group and in 52.8% and 13.5% of participants in the sublingual buprenorphine group, respectively. Among adults with opioid dependence maintaining abstinence with a stable dose of sublingual buprenorphine

  11. Do all screening immunoassay positive buprenorphine samples need to be confirmed?

    Science.gov (United States)

    Saleem, Mohamed; Martin, Helen; Tolya, Anne; Coates, Penny

    2017-11-01

    Background Interference from opiates in the Microgenics CEDIA® Buprenorphine assay is known to produce false-positive buprenorphine screening immunoassay results necessitating confirmatory buprenorphine testing by chromatography/mass spectrometry methods. Method We reviewed data on falsely positive buprenorphine immunoassay screen (cut-off ≥ 5  µg/L) but negative for buprenorphine by gas chromatography mass spectrometry (cut-off ≥ 5  µg/L) and had a positive opiate immunoassay result (cut-off ≥ 300  µg/L). The results were collected over three months, and the data were evaluated to determine whether there is an opiate immunoassay screen concentration below which a false-positive buprenorphine result will not occur. Results We found that cross-reactivity in the CEDIA® buprenorphine immunoassay by opiates at concentrations buprenorphine result. After changing our practice to not proceed with confirmatory buprenorphine gas chromatography mass spectrometry assay when the opiate screening concentration is below an even more conservative cut-off of buprenorphine immunoassay screen do not require confirmatory testing for buprenorphine.

  12. Buprenorphine in the treatment of opioid addiction: opportunities, challenges and strategies.

    Science.gov (United States)

    Li, Xiaofan; Shorter, Daryl; Kosten, Thomas R

    2014-10-01

    Buprenorphine follows the success of methadone as another milestone in the history of treatment for opioid addiction. Buprenorphine can be used in an office-based setting where it is clearly effective, highly accepted by patients and has a favorable safety profile and less abuse potential. However, the adoption of buprenorphine treatment has been slow in the USA. This article first reviews the history of medication-assisted opioid addiction treatment and the current epidemic opioid addiction, followed by a review of the efficacy, pharmacology and clinical prescription of buprenorphine in office-based care. We then explore the possible barriers in using buprenorphine and the ways to overcome these barriers, including new formulations, educational programs and policy regulations that strike a balance between accessibility and reducing diversion. Buprenorphine can align addiction treatment with treatments for other chronic medical illnesses. However, preventing diversion will require graduate and continuing medical education and integrated care models for delivery of buprenorphine to those in need.

  13. Serum concentrations of buprenorphine after oral and parenteral administration in male mice

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Jacobsen, Kirsten R; Hau, Jann

    2011-01-01

    Buprenorphine is the most commonly used drug for peri-operative pain relief in laboratory rodents. The systemic concentrations of buprenorphine were measured in mice following administration intravenously (IV), subcutaneously (SC), orally by gavage and by voluntary ingestion, to determine the post......-administration serum concentration of buprenorphine. Voluntarily ingested buprenorphine resulted in long-lasting high serum concentrations, as did oral gavage administration (24h serum concentration: 110ngh/mL for both routes of administration). In contrast, buprenorphine administered parenterally remained...... of the oral boli, as well as saturation of the hepatic buprenorphine metabolising pathways. Voluntary ingestion of buprenorphine was found to constitute a practical way to provide laboratory mice with efficient pain relief....

  14. Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine

    Energy Technology Data Exchange (ETDEWEB)

    Kahila, H.; Kivitie-Kallio, S.; Halmesmaki, E.; Valanne, L.; Autti, T. [Dept. of Obstetrics and Gynecology, Dept. of Pediatrics, and Helsinki Medical Imaging Center, Helsinki Univ. Central Hospital (Finland)

    2007-02-15

    Purpose: To evaluate the brains of newborns exposed to buprenorphine prenatally. Material and Methods: Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy. Results: Neither structural abnormalities nor abnormalities in signal intensity were recorded. Conclusion: Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic-ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process.

  15. Buprenorphine for cancer pain: is it ready for prime time?

    Science.gov (United States)

    Prommer, Eric

    2015-12-01

    Buprenorphine (BUP) is a semisynthetic derivative of the opium alkaloid thebaine found in the poppy Papaver somniferum. Its chemical structure contains the morphine structure but differs by having a cyclopropylmethyl group. Buprenorphine is a potent µ opioid agonist. Buprenorphine undergoes extensive first-pass metabolism in the liver and gut. The development of a transdermal BUP formulation in 2001 led to its evaluation in cancer pain. This article provides the practitioner with an update on the current role of BUP in cancer care. It highlights data suggesting effectiveness in various types of cancer pain. The article reviews pharmacology, routes of administration, adverse effects, drug interactions, and cost considerations. © The Author(s) 2014.

  16. Sedative and cardiopulmonary effects of buprenorphine and xylazine in horses

    OpenAIRE

    Cruz, Fernando S.F.; Carregaro, Adriano B.; Machado, Melissa; Antonow, Rômulo R.

    2011-01-01

    This study investigated the sedative, cardiopulmonary, and gastrointestinal effects produced by buprenorphine and xylazine given in combination to horses. Six healthy adult horses underwent 4 randomized treatments, with an interval of 1 wk between treatments. A control group was given a saline solution intravenously (IV) and the experimental groups received buprenorphine [10 μg/kg bodyweight (BW)] in combination with 1 of 3 different doses of xylazine: 0.25 mg/kg BW (BX25), 0.50 mg/kg BW (BX5...

  17. Voluntary ingestion of buprenorphine as a refined analgesic strategy

    DEFF Research Database (Denmark)

    Jacobsen, Kirsten Rosenmaj; Kalliokoski, Otto Henrik; Hau, Jann

    2011-01-01

    Buprenorphine is a widely used analgesic for laboratory rodents. Administration of the drug in an attractive food item for voluntary ingestion is a desirable way to administer the drug noninvasively. The method refi nes the standard analgesic procedure and has the potential to improve the welfare...... of laboratory mice and rats. However, many aspects of the voluntary ingestion method still need to be investigated. This paper examines the concept of voluntary ingestion of analgesia and reports new findings about voluntary ingestion of buprenorphine in mice....

  18. Plasma concentrations of buprenorphine following a single subcutaneous administration of a sustained release formulation of buprenorphine in sheep

    OpenAIRE

    Zullian, Chiara; Lema, Pablo; Lavoie, Melissa; Dodelet-Devillers, Aurore; Beaudry, Francis; Vachon, Pascal

    2016-01-01

    The goal of the present study was to evaluate the potential use of slow release buprenorphine in sheep. Twelve adult female sheep (6 Dorset and 6 Suffolk, 12 months of age) were used for this project and were divided into 2 experimental groups (n = 6/group comprising 3 Dorset and 3 Suffolk sheep). Sustained release (SR) buprenorphine was administered subcutaneously in the scapular region at a concentration of 0.1 mg/kg body weight (BW) for group 1 and of 0.05 mg/kg BW for group 2. Following b...

  19. Comparison between analgesic effects of buprenorphine, carprofen, and buprenorphine with carprofen for canine ovariohysterectomy.

    Science.gov (United States)

    Shih, Andre C; Robertson, Sheilah; Isaza, Natalie; Pablo, Luisito; Davies, Wendy

    2008-01-01

    To compare the analgesic effects of buprenorphine, carprofen, and their combination in dogs undergoing ovariohysterectomy. Prospective, randomized blinded clinical study. 60 dogs. Treatments were buprenorphine 0.02 mg kg(-1), intramuscularly (IM) (group B); carprofen 4 mg kg(-1), subcutaneously (SC) (group C); or a combination of both (group CB). Anesthesia was induced with propofol and maintained with isoflurane. A Dynamic Interactive Visual Analog Scale (DIVAS, 0-100 mm) and the Glasgow Composite Pain Scale (GCMPS, 0-24) were used to evaluate comfort and sedation at baseline, 2, 4, 6, and 24 hours after extubation. Rescue analgesia was provided with buprenorphine (0.02 mg kg(-1)). Wound swelling measurements (WM) and a visual inflammation score (VIS) of the incision were made after surgery and 2, 4, 6, and 24 hours later. p < 0.05 was considered significant. Group C required more propofol (5.0 +/- 1.4 mg kg(-1)) compared with B (3.3 +/- 1.1 mg kg(-1)) and CB (3.2 +/- 0.7 mg kg(-1)); respectively, p = 0.0002 and 0.0001. Rescue analgesia was required in nine dogs. B had a higher GCMPS and DIVAS III score at 6 hours (2.6 +/- 2.5) and (23 +/- 22.5 mm) compared with C (1.0 +/- 1.3, 6 +/- 7.3 mm) and CB (1.5 +/- 1.4, 8 +/- 10.7 mm); respectively, p = 0.02 and 0.006. Group C had a lower sedation score at 2 hours (43 +/- 23.6 mm) compared with B (68 +/- 32.1 mm) and BC (69 +/- 22.1 mm); respectively, p = 0.03 and 0.004. Group B had a higher WM score at 2 hours (3 +/- 0.8 mm) compared with C (2 +/- 0.6 mm) p = 0.01 and at 6 hours (3 +/- 1 mm) compared with C (2 +/- 0.8 mm) and CB (2 +/- 0.8 mm); respectively, p = 0.01 and 0.008. VIS was not different between groups. All treatments provided satisfactory analgesia for the first 6 hours and at 24 hours. C and CB pain score and WS were superior to B at 6 hours. No superior analgesic effect was noted when the drugs were combined.

  20. Impact of Medicaid Expansion on Medicaid-covered Utilization of Buprenorphine for Opioid Use Disorder Treatment.

    Science.gov (United States)

    Wen, Hefei; Hockenberry, Jason M; Borders, Tyrone F; Druss, Benjamin G

    2017-04-01

    Buprenorphine has been proven effective in treating opioid use disorder. However, the high cost of buprenorphine and the limited prescribing capacity may restrict access to this effective medication-assisted treatment for opioid use disorder. To examine whether Medicaid expansion and physician prescribing capacity may have impacted buprenorphine utilization covered by Medicaid. We used a quasi experimental difference-in-differences design to compare the pre-post changes in Medicaid-covered buprenorphine prescriptions and buprenorphine spending between the 26 states that implemented Medicaid expansions under the Affordable Care Act in 2014 and those that did not. All Medicaid enrollees in the expansion states and the nonexpansion and late-expansion states. Quarterly Medicaid prescriptions for buprenorphine and spending on buprenorphine from the Centers for Medicare and Medicaid Services Medicaid Drug Utilization files 2011 to 2014. State implementation of Medicaid expansions in 2014 was associated with a 70% increase (Pbuprenorphine prescriptions and a 50% increase (Pbuprenorphine spending. Physician prescribing capacity was also associated with increased buprenorphine utilization. Medicaid expansion has the potential to reduce the financial barriers to buprenorphine utilization and improve access to medication-assisted treatment of opioid use disorder. Active physician participation in the provision of buprenorphine is needed for ensuring that Medicaid expansion achieves its full potential in improving treatment access.

  1. Opioid Abstinence Reinforcement Delays Heroin Lapse during Buprenorphine Dose Tapering

    Science.gov (United States)

    Greenwald, Mark K.

    2008-01-01

    A positive reinforcement contingency increased opioid abstinence during outpatient dose tapering (4, 2, then 0 mg/day during Weeks 1 through 3) in non-treatment-seeking heroin-dependent volunteers who had been maintained on buprenorphine (8 mg/day) during an inpatient research protocol. The control group (n = 12) received $4.00 for completing…

  2. Plasma concentrations of buprenorphine after epidural administration in conscious cats.

    Science.gov (United States)

    Duke-Novakovski, Tanya; Clark, Christopher R; Ambros, Barbara; Gilbert, Peter; Steagall, Paulo V M

    2011-06-01

    Buprenorphine plasma concentrations were measured after administering buprenorphine (20 μg/kg) into the lumbosacral epidural space of conscious cats chronically instrumented with an epidural catheter. Blood was collected from a jugular vein before injection and 15, 30, 45 and 60 min and 2, 3, 4, 5, 6, 8, 12 and 24 h after administration. Plasma buprenorphine concentrations were measured using ELISA. Background concentration (before injection) was 1.27 ± 0.27 ng/mL (mean ± SD). Including background concentration, the mean peak plasma concentration was obtained 15 min after injection (5.82 ± 3.75 ng/mL), and ranged from 3.79 to 2.20 ng/mL (30 min-3 h), remaining between 1.93 and 1.77 ng/mL (4-12 h), and declined to 1.40 ± 0.62 ng/mL at 24h. Elimination half-life was 58.8 ± 40.2 min and clearance 56.7 ± 21.5 mL/min. Results indicate early rapid systemic uptake of buprenorphine from epidural administration with plasma concentrations similar to using buccal or IM routes by 15 min postinjection. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Sedative and cardiopulmonary effects of buprenorphine and xylazine in horses.

    Science.gov (United States)

    Cruz, Fernando S F; Carregaro, Adriano B; Machado, Melissa; Antonow, Rômulo R

    2011-01-01

    This study investigated the sedative, cardiopulmonary, and gastrointestinal effects produced by buprenorphine and xylazine given in combination to horses. Six healthy adult horses underwent 4 randomized treatments, with an interval of 1 wk between treatments. A control group was given a saline solution intravenously (IV) and the experimental groups received buprenorphine [10 μg/kg bodyweight (BW)] in combination with 1 of 3 different doses of xylazine: 0.25 mg/kg BW (BX25), 0.50 mg/kg BW (BX50), or 0.75 mg/kg BW (BX75), all of them by IV. Cardiopulmonary parameters were evaluated for 120 min after the drugs were administered and intestinal motility was observed for 12 h after treatment. Sedation was found to be dose-dependent in all groups receiving buprenorphine and xylazine and it was observed that the heart rate decreased in the first 5 min and increased at the end of the sedation period. Arterial blood gas tension analyses showed minimal alterations during the experiment. Gastrointestinal hypomotility was observed for up to 8 h. The combination of buprenorphine and 0.50 mg/kg BW of xylazine (BX50) provided a 30-minute period of sedation without intense ataxia and maintained cardiopulmonary parameters within acceptable limits for the species.

  4. Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome.

    Science.gov (United States)

    Kraft, Walter K; Adeniyi-Jones, Susan C; Chervoneva, Inna; Greenspan, Jay S; Abatemarco, Diane; Kaltenbach, Karol; Ehrlich, Michelle E

    2017-06-15

    Current pharmacologic treatment of the neonatal abstinence syndrome with morphine is associated with a lengthy duration of therapy and hospitalization. Buprenorphine may be more effective than morphine for this indication. In this single-site, double-blind, double-dummy clinical trial, we randomly assigned 63 term infants (≥37 weeks of gestation) who had been exposed to opioids in utero and who had signs of the neonatal abstinence syndrome to receive either sublingual buprenorphine or oral morphine. Infants with symptoms that were not controlled with the maximum dose of opioid were treated with adjunctive phenobarbital. The primary end point was the duration of treatment for symptoms of neonatal opioid withdrawal. Secondary clinical end points were the length of hospital stay, the percentage of infants who required supplemental treatment with phenobarbital, and safety. The median duration of treatment was significantly shorter with buprenorphine than with morphine (15 days vs. 28 days), as was the median length of hospital stay (21 days vs. 33 days) (Pbuprenorphine group and in 7 of 30 infants (23%) in the morphine group (P=0.36). Rates of adverse events were similar in the two groups. Among infants with the neonatal abstinence syndrome, treatment with sublingual buprenorphine resulted in a shorter duration of treatment and shorter length of hospital stay than treatment with oral morphine, with similar rates of adverse events. (Funded by the National Institute on Drug Abuse; BBORN ClinicalTrials.gov number, NCT01452789 .).

  5. Buprenorphine implants in medical treatment of opioid addiction.

    Science.gov (United States)

    Chavoustie, Steven; Frost, Michael; Snyder, Ole; Owen, Joel; Darwish, Mona; Dammerman, Ryan; Sanjurjo, Victoria

    2017-08-01

    Opioid use disorder is a chronic, relapsing disease that encompasses use of both prescription opioids and heroin and is associated with a high annual rate of overdose deaths. Medical treatment has proven more successful than placebo treatment or psychosocial intervention, and the partial µ-opioid receptor agonist and κ-opioid receptor antagonist buprenorphine is similar in efficacy to methadone while offering lower risk of respiratory depression. However, frequent dosing requirements and potential for misuse and drug diversion contribute to significant complications with treatment adherence for available formulations. Areas covered: This review describes the development of and preliminary data from clinical trials of an implantable buprenorphine formulation. Efficacy and safety data from comparative studies with other administrations of buprenorphine, including tablets and sublingual film, will be described. Key premises of the Risk Evaluation and Mitigation Strategy program for safely administering buprenorphine implants, which all prescribing physicians must complete, are also discussed. Expert commentary: Long-acting implantable drug formulations that offer consistent drug delivery and lower risk of misuse, diversion, or accidental pediatric exposure over traditional formulations represent a promising development for the effective treatment of opioid use disorder.

  6. Opiate withdrawal syndrome in buprenorphine abusers admitted to ...

    African Journals Online (AJOL)

    An ANOVA was conducted to examine the effect of different factors on the withdrawal scores. Results: 32 subjects were included. Among ... The sex v time interaction and the mode of consumption of buprenorphine had significant effects on the withdrawal scores ..... Naloxone reversal of buprenor- phine-induced respiratory ...

  7. Dose-adjusted plasma concentrations of sublingual buprenorphine are lower during than after pregnancy.

    Science.gov (United States)

    Bastian, Jaime R; Chen, Huijun; Zhang, Hongfei; Rothenberger, Scott; Tarter, Ralph; English, Dennis; Venkataramanan, Raman; Caritis, Steve N

    2017-01-01

    Buprenorphine is a Food and Drug Administration-approved maintenance therapy for opioid use disorders and is increasingly being used in pregnant women with opioid use disorders as an alternative to methadone. Dosing of buprenorphine in pregnant women is based on the regimen recommended for nonpregnant females and males. Limited data are available defining the pharmacokinetic properties of sublingual buprenorphine administered during pregnancy. This study evaluated the impact of physiological changes associated with pregnancy on the pharmacokinetics of sublingual buprenorphine during and after pregnancy. Pregnant women (n = 13), between 180/7 and 376/7 weeks' singleton gestation, receiving sublingual buprenorphine twice daily for opioid use disorders were studied. Pharmacokinetic-2 studies were performed between 18 and 25 weeks (n = 7), pharmacokinetic-3 studies were performed between 31 and 37 weeks (n = 11), and pharmacokinetic-P was performed 4-18 weeks postpartum (n = 10). On the day of the study, blood was withdrawn prior to the daily morning dose of buprenorphine and at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, and 12 hours after the dose. Buprenorphine plasma concentrations were analyzed by liquid chromatography tandem mass spectrometric detection. All pharmacokinetic parameters were observed or estimated using Microsoft Excel. Statistical analyses were performed to identify significant changes in study participants' buprenorphine pharmacokinetic parameter estimates over the duration of the study. Univariate linear and generalized linear mixed models were used to investigate changes in these measures over time, some of which were log transformed for normality. Dose-normalized (plasma concentration per dose) buprenorphine plasma concentrations were significantly lower during pregnancy (pharmacokinetic-2 plus pharmacokinetic-3) than during the postpartum period (pharmacokinetic-P). Specific pharmacokinetic parameters (and level of significance) were as follows: the

  8. Discontinuation of Buprenorphine Maintenance Therapy: Perspectives and Outcomes

    Science.gov (United States)

    Bentzley, Brandon S.; Barth, Kelly S.; Back, Sudie E.; Book, Sarah W.

    2015-01-01

    Buprenorphine maintenance therapy (BMT) is increasingly the preferred opioid maintenance agent due to its reduced toxicity and availability in an office-based setting in the United States. Although BMT has been shown to be highly efficacious, it is often discontinued soon after initiation. No current systematic review has yet investigated providers’ or patients’ reasons for BMT discontinuation or the outcomes that follow. Hence, provider and patient perspectives associated with BMT discontinuation after a period of stable buprenorphine maintenance and the resultant outcomes were systematically reviewed with specific emphasis on pre-buprenorphine-taper parameters predictive of relapse following BMT discontinuation. Few identified studies address provider or patient perspectives associated with buprenorphine discontinuation. Within the studies reviewed providers with residency training in BMT were more likely to favor long term BMT instead of detoxification, and providers were likely to consider BMT discontinuation in the face of medication misuse. Patients often desired to remain on BMT because of fear of relapse to illicit opioid use if they were to discontinue BMT. The majority of patients who discontinued BMT did so involuntarily, often due to failure to follow strict program requirements, and 1 month following discontinuation, rates of relapse to illicit opioid use exceeded 50% in every study reviewed. Only lower buprenorphine maintenance dose, which may be a marker for attenuated addiction severity, predicted better outcomes across studies. Relaxed BMT program requirements and frequent counsel on the high probability of relapse if BMT is discontinued may improve retention in treatment and prevent the relapse to illicit opioid use that is likely to follow BMT discontinuation. PMID:25601365

  9. Breakthrough Pain Associated with a Reduction in Serum Buprenorphine Concentration during Dialysis.

    Science.gov (United States)

    Salili, Ali Reza; Müller, Daniel; Skendaj, Roswitha; Jehle, Andreas W; Taegtmeyer, Anne B

    2016-01-01

    To describe a case of breakthrough pain associated with a reduction in serum buprenorphine concentration during dialysis. Pharmacokinetic sampling of total and free buprenorphine and norbuprenorphine in an 80 year old male undergoing haemodialysis three times per week who received 5760 µg oral and transdermal buprenorphine daily was performed. The patient's serum albumin concentration was 23g/l (reference range: 35-52 g/l). Pharmacokinetic sampling revealed a free buprenorphine fraction of 32% (consistent with the hypoalbuminaemia), which was markedly reduced at the end of dialysis (free buprenorphine concentration 2.4 µg/l before vs. buprenorphine doses during dialysis to prevent significant falls in the concentration of active drug. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  10. The antinociceptive efficacy of buprenorphine administered through the drinking water of rats

    DEFF Research Database (Denmark)

    Jessen, L; Bjerrum, Ole Jannik; Christensen, Sten

    2007-01-01

    such as administration of analgesics in the drinking water would be desirable. However, the efficacy of a chronic oral analgesic treatment via this route has not yet been documented. This study investigated the antinociceptive efficacy of buprenorphine administered ad libitum via the drinking water of laboratory rats....... The antinociceptive efficacy of buprenorphine in drinking water was compared with repeated subcutaneous injections. A comparison was also made between buprenorphine in drinking water and the combination of one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water. Antinociception...... was assessed by use of an analgesiometric model measuring the rats' latency time to withdrawal from a noxious heat stimulus applied to the plantar surface of the paw. Results revealed that buprenorphine in drinking water (0.056 mg/mL) induced significant increases in paw withdrawal latency times during a three...

  11. Relationship Between Buprenorphine Dosing and Triglyceride Lowering and Creatinine Kinase Elevation in Felines: Possible Human Implications.

    Science.gov (United States)

    Srinivas, Nuggehally R

    2016-01-01

    Recently published feline data suggest that high doses of buprenorphine can elevate creatinine kinase (CK) and profoundly influence triglyceride levels in an inverted dose versus effect relationship. This intriguing observation in felines, hitherto not documented for buprenorphine, should be considered in human situations for any trends of translatability. The report evaluates the observed effects in domestic cats and what is known about buprenorphine in human subjects. Based on the objective assessment, the following are deduced: (a) although elevated CK levels is a nonissue in humans, one needs to pay attention especially when buprenorphine is used at the high end of therapeutic dose range in the presence of drugs that can impair the hepatic metabolism of buprenorphine; and (b) the potential for triglyceride lowering can be easily confirmed in human trials, and since it may occur at the relevant therapeutic doses of buprenorphine, it may be beneficial in such patients who may have added cardiovascular risk factors.

  12. Quantitation of Total Buprenorphine and Norbuprenorphine in Meconium by LC-MS/MS.

    Science.gov (United States)

    Marin, Stephanie J; McMillin, Gwendolyn A

    2016-01-01

    Buprenorphine (Suboxone, Zubsolv, Buprenex, Butrans, etc.) is an opioid drug that has been used to treat opioid dependence on an outpatient basis, and is also prescribed for managing moderate to severe pain. Pregnant women may be prescribed buprenorphine as part of a treatment plan for opioid addiction. This chapter quantitates buprenorphine and norbuprenorphine in meconium by liquid chromatography tandem mass spectrometry (LC-MS/MS).

  13. Illicit Use of Buprenorphine/Naloxone Among Injecting and Noninjecting Opioid Users

    Science.gov (United States)

    Bazazi, Alexander R.; Yokell, Michael; Fu, Jeannia J.; Rich, Josiah D.; Zaller, Nickolas D.

    2011-01-01

    Objectives We examined the use, procurement, and motivations for the use of diverted buprenorphine/naloxone among injecting and noninjecting opioid users in an urban area. Methods A survey was self-administered among 51 injecting opioid users and 49 noninjecting opioid users in Providence, RI. Participants were recruited from a fixed-site syringe exchange program and a community outreach site between August and November 2009. Results A majority (76%) of participants reported having obtained buprenorphine/naloxone illicitly, with 41% having done so in the previous month. More injection drug users (IDUs) than non-IDUs reported the use of diverted buprenorphine/naloxone (86% vs 65%, P = 0.01). The majority of participants who had used buprenorphine/naloxone reported doing so to treat opioid withdrawal symptoms (74%) or to stop using other opioids (66%) or because they could not afford drug treatment (64%). More IDUs than non-IDUs reported using diverted buprenorphine/naloxone for these reasons. Significantly more non-IDUs than IDUs reported ever using buprenorphine/naloxone to “get high” (69% vs 32%, P buprenorphine/naloxone than in methadone. Common reasons given for not being currently enrolled in a buprenorphine/naloxone program included cost and unavailability of prescribing physicians. Conclusions The use of diverted buprenorphine/naloxone was common in our sample. However, many opioid users, particularly IDUs, were using diverted buprenorphine/naloxone for reasons consistent with its therapeutic purpose, such as alleviating opioid withdrawal symptoms and reducing the use of other opioids. These findings highlight the need to explore the full impact of buprenorphine/naloxone diversion and improve the accessibility of buprenorphine/naloxone through licensed treatment providers. PMID:21844833

  14. Voluntary ingestion of nut paste for administration of buprenorphine in rats and mice

    DEFF Research Database (Denmark)

    Abelson, Klas S P; Jacobsen, Kirsten R; Sundbom, Renée

    2012-01-01

    An adequate analgesic strategy is important to improve the postoperative recovery and welfare of laboratory rats and mice. It is desirable that the method for administering the drug is non-invasive and stress-free. We have previously validated a method for administering buprenorphine in a nut paste...... concentrations and amounts of buprenorphine/nut paste, and dosage of buprenorphine to rats and mice....

  15. Benzodiazepines and alcohol are associated with cases of fatal buprenorphine poisoning.

    Science.gov (United States)

    Häkkinen, Margareeta; Launiainen, Terhi; Vuori, Erkki; Ojanperä, Ilkka

    2012-03-01

    Although buprenorphine therapy has proved to be successful in opioid maintenance treatments, the drug is also widely abused in many countries by intravenous injection or sniffing ("snorting"). In Finland, buprenorphine is the most important abused opioid causing fatal poisonings. To evaluate the drug and alcohol findings as well as the cause and manner of death in all buprenorphine-related post-mortem cases for the age group 14-44 years in Finland from 2000 to 2008. This was a retrospective analysis of data on opioid-associated deaths in the Finnish comprehensive postmortem toxicology database based on medico-legal autopsies, case background information and laboratory analyses. Buprenorphine was found in 29% of all 1,363 opioid-positive cases, and buprenorphine poisoning was the cause of death in 182 cases out of 391 buprenorphine-positive cases (47%). In these fatal poisonings, the blood buprenorphine/norbuprenorphine concentration ratio was significantly higher than in cases with other causes of death. The manner of death in buprenorphine poisonings that were almost exclusively accidental differed significantly from other buprenorphine-related cases, which also involved diseases and suicides. Death was immediate in 10% of fatal buprenorphine poisonings, was delayed, during sleep, in 52%, and followed an unknown course of events in 38%. In immediate poisonings, the median blood buprenorphine concentration (3.0 μg/l) was significantly higher than that in delayed poisonings (1.2 μg/l). In most buprenorphine poisonings (92%), no opioids other than buprenorphine were involved, but benzodiazepines and alcohol were found in 82 and 58% of cases, respectively. The median concentrations of opioids and benzodiazepines in buprenorphine poisonings were in the therapeutic range. Only one fatal poisoning was found in which neither alcohol nor drugs other than buprenorphine were found. A fatal buprenorphine poisoning is typically accidental, and the average victim is a 27

  16. Buprenorphine treatment of opioid-dependent pregnant women: a comprehensive review.

    Science.gov (United States)

    Jones, Hendrée E; Heil, Sarah H; Baewert, Andjela; Arria, Amelia M; Kaltenbach, Karol; Martin, Peter R; Coyle, Mara G; Selby, Peter; Stine, Susan M; Fischer, Gabriele

    2012-11-01

    This paper reviews the published literature regarding outcomes following maternal treatment with buprenorphine in five areas: maternal efficacy, fetal effects, neonatal effects, effects on breast milk and longer-term developmental effects. Within each outcome area, findings are summarized first for the three randomized clinical trials and then for the 44 non-randomized studies (i.e. prospective studies, case reports and series and retrospective chart reviews), only 28 of which involve independent samples. Results indicate that maternal treatment with buprenorphine has comparable efficacy to methadone, although difficulties may exist with current buprenorphine induction methods. The available fetal data suggest buprenorphine results in less physiological suppression of fetal heart rate and movements than methadone. Regarding neonatal effects, perhaps the single definitive conclusion is that prenatal buprenorphine treatment results in a clinically significant less severe neonatal abstinence syndrome (NAS) than treatment with methadone. The limited research suggests that, like methadone, buprenorphine is compatible with breastfeeding. Data available thus far suggest that there are no deleterious effects of in utero buprenorphine exposure on infant development. While buprenorphine produces a less severe neonatal abstinence syndrome than methadone, both methadone and buprenorphine are important parts of a complete comprehensive treatment approach for opioid-dependent pregnant women. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

  17. Postoperative analgesic effects of intravenous, intramuscular, subcutaneous or oral transmucosal buprenorphine administered to cats undergoing ovariohysterectomy.

    Science.gov (United States)

    Giordano, Tatiana; Steagall, Paulo V M; Ferreira, Tatiana H; Minto, Bruno W; de Sá Lorena, Sílvia Elaine Rodolfo; Brondani, Juliana; Luna, Stelio P L

    2010-07-01

    To compare the postoperative analgesic effects of intravenous (IV), intramuscular (IM), subcutaneous (SC) or oral transmucosal (OTM) buprenorphine administered to cats undergoing ovariohysterectomy. Randomized, prospective and blinded clinical trial. 100 female cats. Cats were assigned to receive 0.01 mg kg(-1) of buprenorphine administered by the IV, IM, SC or OTM route (n = 25/group). Buprenorphine was made up to 0.3 mL with 0.9% saline. DIVAS (0-100 mm) and simple descriptive scale (SDS) (from 0 to 4) pain and sedation scores were assigned to each cat before and 1, 2, 3, 4, 6, 8, 12 and 24 hours after ovariohysterectomy. Buprenorphine and carprofen were administered for rescue analgesia. Data were analyzed using anova and Fisher's exact test (p 0.05). There were no significant differences between groups for sedation scores at any time. SDS pain scores did not detect any differences between groups (p > 0.05). DIVAS pain scores after OTM administration were significantly higher than IV and IM administration at 1 hour and at 3, 4, 6, 8 and 12 hours, respectively (p buprenorphine required rescue analgesia, respectively. There was a significantly higher incidence of treatment failure in cats that received SC and OTM buprenorphine compared with cats that received IV and IM buprenorphine (p buprenorphine provided better postoperative analgesia than SC or OTM administration of the drug and these routes of administration should be preferred when buprenorphine is administered to cats.

  18. The applicability of a gel delivery system for self-administration of buprenorphine to laboratory mice

    DEFF Research Database (Denmark)

    Hovard, A. M. B.; Teilmann, A. C.; Hau, J.

    2015-01-01

    ingestion, as well as the amount ingested overnight. Furthermore, buprenorphine in two different concentrations (5 and 15 µg/mL) was mixed in the gel and the resulting serum concentrations of buprenorphine were investigated. The aqueous gel was ingested by the mice, but their willingness was low and did...... not increase over time. The serum concentrations of buprenorphine were similar to, or higher than, those following a subcutaneous injection (0.1 mg/kg body weight), but the variation was considerably higher. In conclusion, aqueous gel may serve as a relevant vehicle for the voluntary ingestion of buprenorphine...

  19. Pharmacodynamic Modelling of Placebo and Buprenorphine Effects on Event-Related Potentials in Experimental Pain

    DEFF Research Database (Denmark)

    Juul, Rasmus V; Foster, David J R; Upton, Richard N

    2014-01-01

    The purpose of the study was to investigate placebo and buprenorphine effects on event-related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volunteers received transdermal placebo and buprenorphine......-effects modelling implemented in NONMEM (V7.2.0.). Pharmacodynamic models were developed to adequately describe both placebo and buprenorphine ERP data. Models predicted significant placebo effects, but did not predict significant effects related to buprenorphine concentration. Models revealed that ERPs varied both...

  20. Interactions Between Buprenorphine and the Protease Inhibitors Darunavir-Ritonavir and Fosamprenavir-Ritonavir

    Science.gov (United States)

    Rainey, Petrie M.; Moody, David E.; Morse, Gene D.; Ma, Qing; Prathikanti, Sudha; Pade, Patricia A.; Alvanzo, Anika A. H.; McCance-Katz, Elinore F.

    2012-01-01

    Background. This study examined drug interactions between buprenorphine, a partial opioid agonist used for opioid dependence treatment and pain management, and the protease inhibitors (PIs) darunavir-ritonavir and fosamprenavir-ritonavir. Methods. The pharmacokinetics of buprenorphine and its metabolites and symptoms of opioid withdrawal or excess were compared in opioid-dependent, buprenorphine-naloxone–maintained, human immunodeficiency virus (HIV)–negative volunteers (11 for darunavir-ritonavir and 10 for fosamprenavir-ritonavir) before and after 15 days of PI administration. PI pharmacokinetics and adverse effects were compared between the buprenorphine-maintained participants and an equal number of sex-, age-, race-, and weight-matched, healthy, non–opioid-dependent volunteers who received darunavir-ritonavir or fosamprenavir-ritonavir but not buprenorphine. Results. There were no significant changes in buprenorphine or PI plasma levels and no significant changes in medication adverse effects or opioid withdrawal. Increased concentrations of the inactive metabolite buprenorphine-3-glucuronide suggested that darunavir-ritonavir and fosamprenavir-ritonavir induced glucuronidation of buprenorphine. Conclusions. Dose adjustments are not likely to be necessary when buprenorphine and darunavir-ritonavir or fosamprenavir-ritonavir are coadministered for the treatment of opioid dependence and HIV disease. PMID:22100576

  1. Advances in the delivery of buprenorphine for opioid dependence

    Directory of Open Access Journals (Sweden)

    Rosenthal RN

    2017-08-01

    Full Text Available Richard N Rosenthal,1 Viral V Goradia2 1Department of Psychiatry, Addiction Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, 2Department of Psychiatry, Upstate Medical University, Syracuse, NY, USA Abstract: Opioid use disorders (OUDs have long been a global problem, but the prevalence rates have increased over 20 years to epidemic proportions in the US, with concomitant increases in morbidity and all-cause mortality, but especially opioid overdose. These increases are in part attributable to a several-fold expansion in the prescription of opioid pain medications over the same time period. Opioid detoxification and psychosocial treatments alone have each not yielded sufficient efficacy for OUD, but μ-opioid receptor agonist, partial agonist, and antagonist medications have demonstrated the greatest overall benefit in OUD treatment. Buprenorphine, a μ-opioid receptor partial agonist, has been used successfully on an international basis for several decades in sublingual tablet and film preparations for the treatment of OUD, but the nature of formulation, which is typically self-administered, renders it susceptible to nonadherence, diversion, and accidental exposure. This article reviews the clinical trial data for novel buprenorphine delivery systems in the form of subcutaneous depot injections, transdermal patches, and subdermal implants for the treatment of OUD and discusses both the clinical efficacy of longer-acting formulations through increasing consistent medication exposure and their potential utility in reducing diversion. These new delivery systems also offer new dosing opportunities for buprenorphine and strategies for dosing intervals in the treatment of OUD. Keywords: opioid use disorder, buprenorphine, drug diversion, drug implants, depot medications, maintenance therapy, treatment adherence

  2. Reversal of stress-induced social interaction deficits by buprenorphine.

    Science.gov (United States)

    Browne, Caroline A; Falcon, Edgardo; Robinson, Shivon A; Berton, Olivier; Lucki, Irwin

    2017-08-31

    Patients with post-traumatic stress disorder (PTSD) frequently report persistent problems with social interactions, emerging after a traumatic experience. Chronic social defeat stress (CSDS) is a widely used rodent model of stress that produces robust and sustained social avoidance behavior. The avoidance of other rodents can be reversed by 28 days of treatment with selective serotonin reuptake inhibitors (SSRIs), the only pharmaceutical class approved by the U. S. Food and Drug Administration for treating PTSD. In this study, the sensitivity of social interaction deficits evoked by 10 days of CSDS to prospective treatments for PTSD was examined. The effects of acute and repeated treatment with a low dose of buprenorphine (0.25 mg/kg/day) on social interaction deficits in male C57BL/6 mice by CSDS were studied. Another cohort of mice was used to determine the effects of the SSRI fluoxetine (10 mg/kg/day), the NMDA antagonist ketamine (10 mg/kg/day) and the selective kappa opioid receptor antagonist CERC-501 (1 mg/kg/day). Changes in mRNA expression of Oprm1 and Oprk1 were assessed in a separate cohort. Buprenorphine significantly reversed social interaction deficits produced by CSDS following 7 days of administration, but not after acute injection. Treatment with fluoxetine for 7 days, but not 24 h, also reinstated social interaction behavior in CSDS-stressed mice. In contrast, CERC-501 and ketamine failed to reverse social avoidance. Gene expression analysis identified reductions in Oprm1 and Oprk1 mRNA expression in the amygdala and hippocampus and increased expression in the frontal cortex in susceptible mice associated with social interaction deficits. Short-term treatment with buprenorphine and fluoxetine normalized social interaction after CSDS. In concert with the changes in opioid receptor expression produced by CSDS, we speculate that buprenorphine's efficacy in this model of PTSD may be associated with the ability of this compound to engage multiple

  3. Successful medical treatment of glans ischemia after voluntary buprenorphine injection.

    Science.gov (United States)

    Brecheteau, François; Grison, Pierre; Abraham, Pierre; Lebdai, Souhil; Kemgang, Steve; Souday, Vincent; Nedelcu, Cosmina; Culty, Thibaut; Larré, Stéphane; Azzouzi, Abdel Rahmene; Bigot, Pierre

    2013-11-01

    The diverted use of synthetic opioid buprenorphine by drug addicts can be responsible for serious ischemic and infectious complications, particularly in the case of intravenous injection. We present a case of serious glans ischemia after buprenorphine injection directly into the deep dorsal vein of the penis. Analysis using new medical imaging techniques and treatments is detailed below. A 26-year-old male drug addict presented with glans pain 4 days after self-injection of buprenorphine into the deep dorsal vein of the penis. The patient was apyretic and presented a urethral discharge. His glans was blue without discoloration on digital pressure. Additionally, his biologic and serologic tests were normal while bacteriology showed the presence of Enterobacter cloacae urethritis. After 48 hours of intravenous antibiotic treatment without improvement, a specific medical treatment using enoxaparin and ilomedin was initiated, with the assumption that there was an ischemic complication. Laser speckle contrast imaging allowed confirmation of the presence of distal penis ischemia and provided an accurate mapping of the ischemic zone. A 28-day treatment combining antibiotics, subcutaneous heparin at curative dose, antiplatelet drug, ilomedin, and hyperbaric oxygen therapy resulted in clinical improvement of the lesions with no functional complications. To date, no consensus exists on the proper diagnostic and treatment approach to severe glans ischemia due to buprenorphine injection into the deep dorsal vein of the penis. The results of laser speckle contrast imaging were of real interest during the process of diagnosis. In addition, the combination of ilomedin with hyperbaric oxygen therapy and anticoagulant and antiplatelet drugs appeared to be an effective therapy. © 2013 International Society for Sexual Medicine.

  4. The switch from buprenorphine to tapentadol: is it worth?

    Science.gov (United States)

    Miclescu, Adriana

    2016-01-01

    Opioid analgesia continues to be the primary pharmacologic intervention for managing acute pain and malignant pain in both hospitalized and ambulatory patients. The increasing use of opioids in chronic nonmalignant pain is more problematic. Opioid treatment is complicated with the risks raised by adverse effects, especially cognitive disturbance, respiratory depression but also the risk of tolerance, opioid abuse and drug–disease interactions. Despite the growing number of available opioids within the last years, adequate trials of opioid rotation are lacking and most of the information is anecdotal. This article reviews the clinical evidence surrounding the switch from transdermal buprenorphine to tapentadol in malignant and non-malignant pain. Tapentadol acts on both the μ-opioid receptors (MOR) and on the neuronal reuptake of noradrenaline with a limited usefulness in acute pain management while buprenorphine is a mixed agonist-antagonist, and both present some advantages over other opioids. Both drugs show particular pharmacodynamic and pharmacokinetic properties which reduce the risks of development of tolerance, opioid abuse, diversion and determine fewer hormone changes than the “classical opioids” making these opioids more attractive than other opioids in long term opioid treatment. However, in the absence of powered clinical trials, the evidence to support the method used for transdermal buprenorphine rotation to tapentadol is weak. PMID:28913486

  5. Investigating medetomidine-buprenorphine as preanaesthetic medication in cats.

    Science.gov (United States)

    Grint, N J; Burford, J; Dugdale, A H A

    2009-02-01

    The objective of this study was to investigate medetomidine-buprenorphine preanaesthetic medication in cats. Forty American Society of Anesthesiologists (ASA) I female cats were enrolled in this prospective, blinded, clinical study. Cats were randomised into one of four groups: group M30 were injected intramuscularly with 30 microg/kg medetomidine, groups M10+B, M30+B and M50+B received 10, 30 and 50 microg/kg of medetomidine, respectively, each in combination with 20 microg/kg buprenorphine. After 30 minutes, a sedation score was allocated. Anaesthesia was induced using intravenous propofol and maintained using isoflurane in oxygen, while cats underwent ovariohysterectomy. Heart rate, respiratory rate, end-tidal carbon dioxide tension and oxygen saturation of haemoglobin were recorded. Atipamezole was administered intramuscularly at volatile agent discontinuation. Time taken to lift their head, sit in sternal and stand were recorded along with quality of recovery. M30+B cats required significantly less isoflurane compared with M30 cats. Heart rate and oxygen saturation of haemoglobin were significantly lower in M50+B cats than in M30 cats. All M+B groups experienced significantly better recoveries compared with the medetomidine only M30 control group. The addition of buprenorphine to medetomidine preanaesthetic medication in cats reduces volatile agent vaporiser setting and improves the quality of recovery from anaesthesia.

  6. Depression-Like Effect of Prenatal Buprenorphine Exposure in Rats

    Science.gov (United States)

    Hung, Chih-Jen; Wu, Chih-Cheng; Chen, Wen-Ying; Chang, Cheng-Yi; Kuan, Yu-Hsiang; Pan, Hung-Chuan; Liao, Su-Lan; Chen, Chun-Jung

    2013-01-01

    Studies indicate that perinatal opioid exposure produces a variety of short- and long-term neurobehavioral consequences. However, the precise modes of action are incompletely understood. Buprenorphine, a mixed agonist/antagonist at the opioid receptors, is currently being used in clinical trials for managing pregnant opioid addicts. This study provides evidence of depression-like consequence following prenatal exposure to supra-therapeutic dose of buprenorphine and sheds light on potential mechanisms of action in a rat model involving administration of intraperitoneal injection to pregnant Sprague-Dawley rats starting from gestation day 7 and lasting for 14 days. Results showed that pups at postnatal day 21 but not the dams had worse parameters of depression-like neurobehaviors using a forced swimming test and tail suspension test, independent of gender. Neurobehavioral changes were accompanied by elevation of oxidative stress, reduction of plasma levels of brain-derived neurotrophic factor (BDNF) and serotonin, and attenuation of tropomyosin-related kinase receptor type B (TrkB) phosphorylation, extracellular signal-regulated kinase (ERK) phosphorylation, protein kinase A activity, cAMP response element-binding protein (CREB) phosphorylation, and CREB DNA-binding activity. Since BDNF/serotonin and CREB signaling could orchestrate a positive feedback loop, our findings suggest that the induction of oxidative stress, reduction of BDNF and serotonin expression, and attenuation of CREB signaling induced by prenatal exposure to supra-therapeutic dose of buprenorphine provide evidence of potential mechanism for the development of depression-like neurobehavior. PMID:24367510

  7. Pharmacokinetics of intravenous and intramuscular buprenorphine in the horse.

    Science.gov (United States)

    Davis, J L; Messenger, K M; LaFevers, D H; Barlow, B M; Posner, L P

    2012-02-01

    The purpose of this study was to determine the pharmacokinetics of buprenorphine following intravenous (i.v.) and intramuscular (i.m.) administration in horses. Six horses received i.v. or i.m. buprenorphine (0.005 mg/kg) in a randomized, crossover design. Plasma samples were collected at predetermined times and horses were monitored for adverse reactions. Buprenorphine concentrations were measured using ultra-performance liquid chromatography with electrospray ionization mass spectrometry. Following i.v. administration, clearance was 7.97±5.16 mL/kg/min, and half-life (T(1/2)) was 3.58 h (harmonic mean). Volume of distribution was 3.01±1.69 L/kg. Following i.m. administration, maximum concentration (C(max)) was 1.74±0.09 ng/mL, which was significantly lower than the highest measured concentration (4.34±1.22 ng/mL) after i.v. administration (PBuprenorphine has a moderate T(1/2) in the horse and was detected at concentrations expected to be therapeutic in other species after i.v. and i.m. administration of 0.005 mg/kg. Signs of excitement and gastrointestinal stasis may be noted. © 2011 Blackwell Publishing Ltd.

  8. Depression-like effect of prenatal buprenorphine exposure in rats.

    Directory of Open Access Journals (Sweden)

    Chih-Jen Hung

    Full Text Available Studies indicate that perinatal opioid exposure produces a variety of short- and long-term neurobehavioral consequences. However, the precise modes of action are incompletely understood. Buprenorphine, a mixed agonist/antagonist at the opioid receptors, is currently being used in clinical trials for managing pregnant opioid addicts. This study provides evidence of depression-like consequence following prenatal exposure to supra-therapeutic dose of buprenorphine and sheds light on potential mechanisms of action in a rat model involving administration of intraperitoneal injection to pregnant Sprague-Dawley rats starting from gestation day 7 and lasting for 14 days. Results showed that pups at postnatal day 21 but not the dams had worse parameters of depression-like neurobehaviors using a forced swimming test and tail suspension test, independent of gender. Neurobehavioral changes were accompanied by elevation of oxidative stress, reduction of plasma levels of brain-derived neurotrophic factor (BDNF and serotonin, and attenuation of tropomyosin-related kinase receptor type B (TrkB phosphorylation, extracellular signal-regulated kinase (ERK phosphorylation, protein kinase A activity, cAMP response element-binding protein (CREB phosphorylation, and CREB DNA-binding activity. Since BDNF/serotonin and CREB signaling could orchestrate a positive feedback loop, our findings suggest that the induction of oxidative stress, reduction of BDNF and serotonin expression, and attenuation of CREB signaling induced by prenatal exposure to supra-therapeutic dose of buprenorphine provide evidence of potential mechanism for the development of depression-like neurobehavior.

  9. SUBLINGUAL BUPRENORPHINE VS MIDAZOLAM FOR PREMEDICATION IN CHILDREN

    Directory of Open Access Journals (Sweden)

    V.A HASANI

    2000-03-01

    Full Text Available Background. Preanesthetic medication may reduce the risks of adverse psychological and physiological sequel of induction in children. Administration of premedication by sublingual route may provide the best compromise because of relatively rapid absorption without causing pain. In this study sedative and anxitolytic effects of sublingual midazolam and buprenorphine in children were compared. Methods. In a randomized, controlled, double blind clinical trial, one hundred and fifty children aged between 4 to 10 years in first or second class of ASA scheduled for adenotonsillectomy were divided in three equal groups. These groups recieved sublingual bupronorphine 3 µg/kg, midazolam 0.2 mg/kg and no premedication respectively. Cardiorespiratory variables were recorded from the time of premedication to awakening from anesthesia. Anxiety and sedation scores and patients acceptance of mask at induction were recorded using four point rating scales. Time of spontaneous eye opening and postoperative emesis occurrence were also recorded. Findings. Children recieving sublingual midazolam or buprenorphine had similar sedation, anxiety and mask acceptance scores, but different from no premedication group (P < 0.0001. None of the children experienced respiratory depression or oxygen desaturation after drug administration and during postoperative period. Time of spontaneous eye opening was longer in the midazolam group (P < 0.0001.Emetic episodes were similar in all groups. Conclusion. Midazolam is extensively studied and demonstrated that the drug is highly effective in alleviating anxiety and increasing cooperation. We concluded that sublingual buprenorphine is as effective as sublingual midazolam in providing sedation and anxitolysis for pediatric premedication.

  10. Parenting and concerns of pregnant women in buprenorphine treatment.

    Science.gov (United States)

    Rizzo, Rachel A; Neumann, Anne M; King, Stella O C; Hoey, Robert F; Finnell, Deborah S; Blondell, Richard D

    2014-01-01

    Opioid-dependent pregnant women are characterized by drug use during pregnancy and deficits in knowledge of newborn care and feeding, and of child development. We assessed parenting skills and concerns among pregnant women in buprenorphine treatment for prescription opioid dependence. We interviewed 32 pregnant women who received buprenorphine treatment for prescription opioid dependence in a primary care setting and administered questionnaires, including the Adult-Adolescent Parenting Inventory version 2 (AAPI-2) and Childhood Experience of Care and Abuse Questionnaire. AAPI-2 scores revealed medium risk of abuse for all five scales: inappropriate expectations of the child, low level of empathy, strong belief in corporal punishment, reversal of parent-child roles, and oppression of children's power and independence. Primary concerns of participants were neonatal abstinence syndrome (NAS) and their child's health. Pregnant women who received buprenorphine for treatment of prescription opioid dependence showed a lack of appropriate parenting skills, but did not express concern about their ability to parent. Our findings suggest a need for nurses to assist prescription opioid-dependent pregnant women in acquiring additional parenting skills, to refer for educational parenting intervention, and to educate patients about NAS.

  11. Double-blind, multiple-dose comparison of buprenorphine and morphine in postoperative pain.

    Science.gov (United States)

    Tigerstedt, I; Tammisto, T

    1980-12-01

    The analgesic profile and side-effects of buprenorphine 0.3 mg and morphine 10 mg intramuscularly were compared postoperatively in a double-blind, non-crossover, multiple-dose study. When the patient complained of moderate to severe postoperative pain after halothane-relaxant anesthesia for upper abdominal surgery, the first test dose of either drug was given. Subsequent similar doses of buprenorphine 0.3 mg or morphine 10 mg were given when required (maximum ten doses). The first dose of both drugs gave an equal decrease in pain intensity, suggesting a relative potency of 33:1 for both buprenorphine/morphine. A mean of 0.51 mg buprenorphine or 17 mg morphine had to be administered for satisfactory initial analgesia. Thereafter, the next analgesic dose was required a mean of 10.3 h after buprenorphine compared to 5.9 h after morphine (P less than 0.01). Significantly (P less than 0.01) fewer analgesic doses (mean 5.6) were needed in the buprenorphine group within the first 48 h postoperatively as compared to the morphine group (mean 7.3). A more pronounced mean decrease in the respiratory rate was observed after buprenorphine, but the mean minimum respiratory rates did not differ significantly from each other. Other effects of the two drugs on vital signs were similar. The incidence of other side-effects was fairly similar after both analgesics. The patients' subjective appraisal favoured buprenorphine.

  12. Evaluation of thermal antinociceptive effects after intramuscular administration of buprenorphine hydrochloride to American kestrels (Falco sparverius).

    Science.gov (United States)

    Ceulemans, Susanne M; Guzman, David Sanchez-Migallon; Olsen, Glenn H; Beaufrère, Hugues; Paul-Murphy, Joanne R

    2014-08-01

    To evaluate the thermal antinociceptive effects and duration of action of buprenorphine hydrochloride after IM administration to American kestrels (Falco sparverius). 12 healthy 3-year-old American kestrels. Buprenorphine hydrochloride (0.1, 0.3, and 0.6 mg/kg) and a control treatment (saline [0.9% NaCl] solution) were administered IM in a randomized crossover experimental design. Foot withdrawal response to a thermal stimulus was determined 1 hour before (baseline) and 1.5, 3, and 6 hours after treatment administration. Agitation-sedation scores were determined 3 to 5 minutes before each thermal stimulus. Adverse effects were monitored for 6 hours after treatment administration. Buprenorphine hydrochloride at 0.1, 0.3, and 0.6 mg/kg, IM, increased thermal threshold for 6 hours, compared with the response for the control treatment. There were no significant differences among buprenorphine treatments. A mild sedative effect was detected at a dose of 0.6 mg of buprenorphine/kg. At the doses tested, buprenorphine hydrochloride resulted in thermal antinociception in American kestrels for at least 6 hours, which suggested that buprenorphine has analgesic effects in this species. Further studies with longer evaluation periods and additional forms of noxious stimuli, formulations, dosages, and routes of administration are needed to fully evaluate the analgesic effects of buprenorphine in American kestrels.

  13. Antinociceptive effect of buprenorphine and evaluation of the nociceptive withdrawal reflex in foals.

    Science.gov (United States)

    Risberg, Åse I; Spadavecchia, Claudia; Ranheim, Birgit; Hendrickson, Eli H S; Lervik, Andreas; Haga, Henning A

    2015-05-01

    To elicit and evaluate the NWR (nociceptive withdrawal reflex) in 2 and 11 day old foals, to investigate if buprenorphine causes antinociception and determine if the NWR response changes with increasing age. The effect of buprenorphine on behaviour was also evaluated. Prospective, experimental cross-over trial. Nine Norwegian Fjord research foals. Buprenorphine, 10 μg kg(-1) was administered intramuscularly (IM) to the same foal at 2 days and at 11 days of age. The NWR and the effect of buprenorphine were evaluated by electromyograms recorded from the left deltoid muscle following electrical stimulation of the left lateral palmar nerve at the level of the pastern. Mentation, locomotor activity and respiratory rate were recorded before and after buprenorphine administration. We were able to evoke the NWR and temporal summation in foals using this model. Buprenorphine decreased the root mean square amplitude following single electrical stimulation (p buprenorphine. These findings indicate that buprenorphine has antinociceptive effect in foals. Opioid side effects often recognized in adult horses also occur in foals. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  14. Prior Experience with Non-Prescribed Buprenorphine: Role in Treatment Entry and Retention.

    Science.gov (United States)

    Monico, Laura B; Mitchell, Shannon Gwin; Gryczynski, Jan; Schwartz, Robert P; O'Grady, Kevin E; Olsen, Yngvild K; Jaffe, Jerome H

    2015-10-01

    Buprenorphine availability continues to expand as an effective treatment for opioid dependence, but increases in availability have also been accompanied by increases in non-prescribed use of the medication. Utilizing data from a randomized clinical trial, this mixed-method study examines associations between use of non-prescribed buprenorphine and subsequent treatment entry and retention. Quantitative analyses (N = 300 African American buprenorphine patients) found that patients with prior use of non-prescribed buprenorphine had significantly higher odds of remaining in treatment through 6 months than patients who were naïve to the medication upon treatment entry. Qualitative data, collected from a subsample of participants (n = 20), identified three thematic explanations for this phenomenon: 1) perceived effectiveness of the medication; 2) cost of obtaining prescription buprenorphine compared to purchasing non-prescribed medication; and 3) convenience of obtaining the medication via daily-dosing or by prescription compared to non-prescribed buprenorphine. These findings suggest a dynamic relationship between non-prescribed buprenorphine use and treatment that indicates potential directions for future research into positive and negative consequences of buprenorphine diversion. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Buprenorphine Treatment of Opioid-Dependent Pregnant Women: A Comprehensive Review

    Science.gov (United States)

    Jones, Hendrée E.; Arria, Amelia M.; Baewert, Andjela; Heil, Sarah H.; Kaltenbach, Karol; Martin, Peter R.; Coyle, Mara G.; Selby, Peter; Stine, Susan M.; Fischer, Gabriele

    2015-01-01

    Aims This paper reviews the published literature regarding outcomes following maternal treatment with buprenorphine in five areas: maternal efficacy, fetal effects, neonatal effects, effects on breast milk, and longer-term developmental effects. Methods Within each outcome area, findings are summarized first for the 3 randomized controlled trials and then for the 44 non-randomized studies (i.e., prospective studies, case reports and series, and retrospective chart reviews), only 28 of which involve independent samples. Results Results indicate that maternal treatment with buprenorphine has comparable efficacy to methadone, although difficulties may exist with current buprenorphine induction methods. The available fetal data suggest buprenorphine results in less physiologic suppression of fetal heart rate and movements than methadone. Regarding neonatal effects, perhaps the single definitive conclusion is that prenatal buprenorphine treatment results in a clinically significant less severe neonatal abstinence syndrome (NAS) than treatment with methadone. The limited research suggests that, like methadone, buprenorphine is compatible with breastfeeding. Data available thus far suggest that there are no deleterious effects of in utero buprenorphine exposure on infant development. Conclusions Buprenorphine produces a less severe neonatal abstinence syndrome than methadone, but there is still a role for methadone in the treatment of opioid dependence during pregnancy. PMID:23106923

  16. Optimizing psychosocial support during office-based buprenorphine treatment in primary care: Patients' experiences and preferences.

    Science.gov (United States)

    Fox, Aaron D; Masyukova, Mariya; Cunningham, Chinazo O

    2016-01-01

    Buprenorphine maintenance treatment is effective and has been successfully integrated into human immunodeficiency virus (HIV) and primary care settings. However, one key barrier to providers prescribing buprenorphine is their perception that they are unable to provide adequate counseling or psychosocial support to patients with opioid addiction. This qualitative study investigated supportive elements of office-based buprenorphine treatment that patients perceived to be most valuable. The authors conducted five focus groups with 33 buprenorphine treatment-experienced participants. Focus groups were audio-recorded and transcribed. Iterative readings of transcripts and grounded theory analysis revealed common themes. Overall, participants perceived that buprenorphine treatment helped them to achieve their treatment goals and valued the flexibility, accessibility, and privacy of treatment. Participants identified interpersonal and structural elements of buprenorphine treatment that provided psychosocial support. Participants desired good physician-patient relationships, but also valued care delivery models that were patient-centered, created a safe place for self-disclosure, and utilized coordinated team-based care. Participants derived psychosocial support from their prescribing physician, but were also open to collaborative or team-based models of care, as long as they were voluntary and confidential. Buprenorphine-prescribing physicians without access to referral options for psychosocial counseling could focus on maintaining nonjudgmental attitudes and shared decision-making during patient encounters. Adding structure and psychosocial support to buprenorphine treatment through coordinated team-based care also seems to have great promise.

  17. PREVALENCE AND CORRELATES OF STREET-OBTAINED BUPRENORPHINE USE AMONG CURRENT AND FORMER INJECTORS IN BALTIMORE, MARYLAND

    Science.gov (United States)

    Genberg, Becky L.; Gillespie, Mirinda; Schuster, Charles R.; Johanson, Chris-Ellyn; Astemborski, Jacquie; Kirk, Gregory D.; Vlahov, David; Mehta, Shruti H.

    2013-01-01

    Objectives There are few systematic assessments of street-obtained buprenorphine use from community-based samples in the United States. The objective of this study was to characterize the prevalence, correlates, and reasons for street-obtained buprenorphine use among current and former injection drug users (IDUs) in Baltimore, Maryland. Methods In 2008, participants of the ALIVE (AIDS Linked to the IntraVenous Experience) study, a community-based cohort of IDUs, were administered a survey on buprenorphine. Street-obtained buprenorphine represented self-reported use of buprenorphine obtained from the street or a friend in the prior three months. Results 602 respondents were predominantly male (65%), African-American (91%), and 30% were HIV-positive. Overall, nine percent reported recent street-obtained buprenorphine use, and only 2% reported using to get high. Among active opiate users, 23% reported recent use of street-obtained buprenorphine. Use of buprenorphine prescribed by a physician, injection and non-injection drug use, use of street-obtained methadone and prescription opiates, homelessness, and opioid withdrawal symptoms were positively associated, while methadone treatment, health insurance, outpatient care, and HIV-infection were negatively associated with recent street-obtained buprenorphine use in univariate analysis. After adjustment, active injection and heroin use were positively associated with street-obtained buprenorphine use. Ninety-one percent reported using street-obtained buprenorphine to manage withdrawal symptoms. Conclusions While 9% reported recent street-obtained buprenorphine use, only a small minority reported using buprenorphine to get high, with the majority reporting use to manage withdrawal symptoms. There is limited evidence of diversion of buprenorphine in this sample and efforts to expand buprenorphine treatment should continue with further monitoring. PMID:24018232

  18. Two doses of dexmedetomidine in combination with buprenorphine for premedication in dogs; a comparison with acepromazine and buprenorphine.

    Science.gov (United States)

    Bell, Andrew M; Auckburally, Adam; Pawson, Patricia; Scott, E Marian; Flaherty, Derek

    2011-01-01

    To assess as premedicants, the sedative, cardiorespiratory and propofol-sparing effects in dogs of dexmedetomidine and buprenorphine compared to acepromazine and buprenorphine. Prospective, randomised, blinded clinical study. Sixty healthy dogs (ASA grades I/II). Mean (SD) body mass 28.0 ± 9.1 kg, and mean age 3.4 ± 2.3 years.   Dogs were allocated randomly to receive 15 μg kg(-1) buprenorphine combined with either 30 μg kg(-1) acepromazine (group 1), 62.5 μg m(-2) dexmedetomidine (group 2), or 125 μg m(-2) dexmedetomidine (group 3) intramuscularly. After 30 minutes, anaesthesia was induced using a propofol target controlled infusion. Heart rate, respiratory rate, and oscillometric arterial blood pressure were recorded prior to induction, at endotracheal intubation and at 3 and 5 minutes post-intubation. Induction quality and pre-induction sedation were scored on 4 point scales. Propofol target required for endotracheal intubation was recorded. Data were analysed using Chi-squared tests, Kruskal-Wallis, one way and general linear model ANOVA (pbuprenorphine, at these doses, dexmedetomidine had no advantages in terms of sedation and induction quality over acepromazine. Both doses of dexmedetomidine produced characteristic cardiovascular and respiratory effects of a similar magnitude. © 2011 The Authors. Veterinary Anaesthesia and Analgesia © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  19. UHPLC-MS/MS quantification of buprenorphine, norbuprenorphine, methadone, and glucuronide conjugates in umbilical cord plasma.

    Science.gov (United States)

    Kyle, Amy Redmond; Carmical, Jennifer; Shah, Darshan; Pryor, Jason; Brown, Stacy

    2015-10-01

    Opioid use during pregnancy can result in the newborn being physically dependent on the substance, thus experiencing drug withdrawal, termed neonatal abstinence syndrome (NAS). Buprenorphine and methadone are two drugs used to treat opioid withdrawal and are approved for use in pregnancy. Quantification of these compounds in umbilical cord plasma would help assess in utero exposure of neonates in cases of buprenorphine or methadone use during pregnancy. An LC-MS/MS method using solid-phase extraction sample preparation was developed and validated for the simultaneous quantification of methadone, buprenorphine, norbuprenorphine, and glucuronide metabolites in umbilical cord plasma. The average accuracy (percentage error) and precision (relative standard deviation) were buprenorphine and metabolite concentrations. This method was successfully applied to the analysis of cord blood from women with known buprenorphine or methadone use during pregnancy. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Plasma concentrations of corticosterone and buprenorphine in rats subjected to jugular vein catheterization

    DEFF Research Database (Denmark)

    Goldkuhl, Renée; Jacobsen, Kirsten Rosenmaj; Kalliokoski, Otto Henrik

    2010-01-01

    The present study investigated the postoperative plasma concentrations of corticosterone and buprenorphine in male Wistar and Sprague-Dawley rats, treated with buprenorphine administered either through subcutaneous (SC) injection or through voluntary ingestion (VI). The animals were treated...... with buprenorphine for pre-emptive analgesia prior to surgical placement of a jugular catheter, followed by automated blood sampling during 96 h. Buprenorphine was administered on a regular basis throughout the experiment, and blood was collected on selected time points. Body weight was measured before and 96 h...... after surgery. It was found that the two rat stocks responded in a similar manner to both buprenorphine treatments, with the exception of body weight change in Wistar rats, in which body weight was reduced after SC treatment. The plasma concentration of corticosterone was significantly higher in the SC...

  1. Training in Buprenorphine and Office-Based Opioid Treatment: A Survey of Psychiatry Residency Training Programs.

    Science.gov (United States)

    Suzuki, Joji; Ellison, Tatyana V; Connery, Hilary S; Surber, Charles; Renner, John A

    2016-06-01

    Psychiatrists are well suited to provide office-based opioid treatment (OBOT), but the extent to which psychiatry residents are exposed to buprenorphine training and OBOT during residency remains unknown. Psychiatry residency programs in the USA were recruited to complete a survey. Forty-one programs were included in the analysis for a response rate of 23.7 %. In total, 75.6 % of the programs currently offered buprenorphine waiver training and 78.1 % provided opportunities to treat opioid dependence with buprenorphine under supervision. Programs generally not only reported favorable beliefs about OBOT and buprenorphine waiver training but also reported numerous barriers. The majority of psychiatry residency training programs responding to this survey offer buprenorphine waiver training and opportunities to treat opioid-dependent patients, but numerous barriers continue to be cited. More research is needed to understand the role residency training plays in impacting future practice of psychiatrists.

  2. The New Kid on the Block--Incorporating Buprenorphine into a Medical Toxicology Practice.

    Science.gov (United States)

    Wiegand, Timothy J

    2016-03-01

    Buprenorphine represents a safe and effective therapy for treating opioid dependence, alleviating craving and withdrawal symptoms in opioid-dependent patients. Buprenorphine has a "blocking" effect against the action of other opioids at the mu-receptor, preventing not only opioid-induced euphoria, but CNS and respiratory depressant effects as well. Buprenorphine was approved for the treatment of opioid dependence in 2002 after the passage of Drug Abuse Treatment Act 2000 (DATA 2000) which allowed clinicians to treat opioid-dependent patients with specifically named opioid agonist therapies in an office setting. Buprenorphine programs reduce the prevalence of HIV and hepatitis C and reduce criminal behaviors associated with illicit drug use. Patients stabilized on buprenorphine have increased employment, enhanced engagement with social services, and better overall health and well-being.

  3. Mediation of buprenorphine analgesia by a combination of traditional and truncated mu opioid receptor splice variants.

    Science.gov (United States)

    Grinnell, Steven G; Ansonoff, Michael; Marrone, Gina F; Lu, Zhigang; Narayan, Ankita; Xu, Jin; Rossi, Grace; Majumdar, Susruta; Pan, Ying-Xian; Bassoni, Daniel L; Pintar, John; Pasternak, Gavril W

    2016-10-01

    Buprenorphine has long been classified as a mu analgesic, although its high affinity for other opioid receptor classes and the orphanin FQ/nociceptin ORL1 receptor may contribute to its other actions. The current studies confirmed a mu mechanism for buprenorphine analgesia, implicating several subsets of mu receptor splice variants. Buprenorphine analgesia depended on the expression of both exon 1-associated traditional full length 7 transmembrane (7TM) and exon 11-associated truncated 6 transmembrane (6TM) MOR-1 variants. In genetic models, disruption of delta, kappa1 or ORL1 receptors had no impact on buprenorphine analgesia, while loss of the traditional 7TM MOR-1 variants in an exon 1 knockout (KO) mouse markedly lowered buprenorphine analgesia. Loss of the truncated 6TM variants in an exon 11 KO mouse totally eliminated buprenorphine analgesia. In distinction to analgesia, the inhibition of gastrointestinal transit and stimulation of locomotor activity were independent of truncated 6TM variants. Restoring expression of a 6TM variant with a lentivirus rescued buprenorphine analgesia in an exon 11 KO mouse that still expressed the 7TM variants. Despite a potent and robust stimulation of (35) S-GTPγS binding in MOR-1 expressing CHO cells, buprenorphine failed to recruit β-arrestin-2 binding at doses as high as 10 µM. Buprenorphine was an antagonist in DOR-1 expressing cells and an inverse agonist in KOR-1 cells. Buprenorphine analgesia is complex and requires multiple mu receptor splice variant classes but other actions may involve alternative receptors. © 2016 Wiley Periodicals, Inc.

  4. A Combination of Buprenorphine and Naltrexone Blocks Compulsive Cocaine Intake in Rodents Without Producing Dependence

    Science.gov (United States)

    Wee, Sunmee; Vendruscolo, Leandro F.; Misra, Kaushik K.; Schlosburg, Joel E.; Koob, George F.

    2012-01-01

    Buprenorphine, a synthetic opioid that acts at both μ and κ opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at μ opioid receptors raises its potential for creating opioid dependence in non–opioid-dependent cocaine abusers. Here, we tested the hypothesis that a combination of buprenorphine and naltrexone (a potent μ opioid antagonist with weaker δ and κ antagonist properties) could block compulsive cocaine self-administration without producing opioid dependence. The effects of buprenorphine and various doses of naltrexone on cocaine self-administration were assessed in rats that self-administered cocaine under conditions of either short access (noncompulsive cocaine seeking) or extended access (compulsive cocaine seeking). Buprenorphine alone reproducibly decreased cocaine self-administration. Although this buprenorphine-alone effect was blocked in a dose-dependent manner by naltrexone in both the short-access and the extended-access groups, the combination of the lowest dose of naltrexone with buprenorphine blocked cocaine self-administration in the extended-access group but not in the short-access group. Rats given this low dose of naltrexone with buprenorphine did not exhibit the physical opioid withdrawal syndrome seen in rats treated with buprenorphine alone, and naltrexone at this dose did not block κ agonist–induced analgesia. The results suggest that the combination of buprenorphine and naltrexone at an appropriate dosage decreases compulsive cocaine self-administration with minimal liability to produce opioid dependence and may be useful as a treatment for cocaine addiction. PMID:22875830

  5. Does concurrent in utero exposure to buprenorphine and antidepressant medications influence the course of neonatal abstinence syndrome?

    Science.gov (United States)

    O'Connor, Alane B; O'Brien, Liam; Alto, William A; Wong, Jacqueline

    2016-01-01

    To determine whether concurrent in utero exposure to buprenorphine and antidepressants impacts the course of neonatal abstinence syndrome (NAS) in infants. A retrospective cohort study of 148 infants who were exposed to buprenorphine during pregnancy. Univariate and bivariate analyses were used to examine associations between concurrent maternal use of buprenorphine and antidepressants as compared to maternal use of buprenorphine alone. The time to onset of NAS resolution was significantly longer in infants exposed to both buprenorphine and antidepressants during pregnancy when compared to those exposed to buprenorphine alone (129.8 h versus 70.2 h, p = 0.042). Women who are prescribed both antidepressants and buprenorphine during pregnancy should be counseled about the possibility of a prolonged course of neonatal abstinence syndrome.

  6. Buprenorphine – an attractive opioid with underutilized potential in treatment of chronic pain

    Directory of Open Access Journals (Sweden)

    Khanna IK

    2015-12-01

    Full Text Available Ish K Khanna, Sivaram PillarisettiNeuroPn Therapeutics, Alpharetta, GA, USAAbstract: Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about “ceiling effect” or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed µ-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and noncancer pain. Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs marketed opioids. No ceiling on analgesic effect has been reported in clinical studies. The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. The buprenorphine pharmacology also allows it to be combined with other µ-receptor opioids for additivity in efficacy. Transdermal delivery products of buprenorphine have been preferred choices for the management of pain but new delivery options are under investigation for the treatment of both opioid dependence and chronic pain.Keywords: buprenorphine, opioids, opioid dependence, partial agonist, hyperalgesia, neuropathic pain

  7. Radioimmunoassay of buprenorphine in urine: Studies in patients and in a drug clinic

    Energy Technology Data Exchange (ETDEWEB)

    Hand, C.W.; Ryan, K.E.; Dutt, S.K.; Moore, R.A. (DPC European Research Institute, Witney (England)); O' Connor, J.; Talbot, D. (Jervis Street Hospital, Dublin (Ireland)); McQuay, H.J. (Abingdon Hospital, Oxford (England))

    A radioimmunoassay kit (DPC buprenorphine double antibody) was evaluated with clinical samples and samples from a drug clinic. Urine samples were collected over a 2-day period from 5 hospital in-patients receiving sublingual buprenorphine, 400 to 2000 {mu}g/day, for the relief of chronic pain. Samples were measured before and after enzymatic hydrolysis. Urine buprenorphine concentrations were measurable at all doses studied (minimum value 5.6 ng/mL) and were greater with larger doses. The increase in concentration after hydrolysis averaged 49% and was similar for all doses studied. The authors conclude that the method has extensive cross-reactivity with glucuronides of buprenorphine and its metabolites and that samples may be analyzed without prior hydrolysis. The prevalence of buprenorphine use in 97 patients attending a drug clinic was also studied. Sixty (62%) had measurable urinary buprenorphine concentrations of 1 ng/mL or more by direct assay. The buprenorphine users were significantly younger and reported significantly greater use of opiates than nonusers.

  8. Buprenorphine physician supply: Relationship with state-level prescription opioid mortality.

    Science.gov (United States)

    Knudsen, Hannah K; Havens, Jennifer R; Lofwall, Michelle R; Studts, Jamie L; Walsh, Sharon L

    2017-04-01

    Buprenorphine is an effective treatment for opioid use disorder but the supply of buprenorphine physicians is currently inadequate to address the nation's prescription opioid crisis. Perception of need due to rising opioid overdose rates is one possible reason for physicians to adopt buprenorphine. This study examined associations between rates of growth in buprenorphine physicians and prescription opioid overdose mortality rates in US states. The total buprenorphine physician supply and number of physicians approved to treat 100 patients (per 100,000 population) were measured from June 2013 to January 2016. States were divided into two groups: those with rates of prescription opioid overdose mortality in 2013 at or above the median (>5.5 deaths per 100,000 population) and those with rates below the median. State-level growth curves were estimated using mixed-effects regression to compare rates of growth between high and low overdose states. The total supply and the supply of 100-patient buprenorphine physicians grew significantly (total supply from 7.7 to 9.9 per 100,000 population, pbuprenorphine physicians. Because this observational design cannot establish causality, further research is needed to elucidate the factors influencing physicians' decisions to begin prescribing buprenorphine. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  9. Buprenorphine Maintenance for Opioid Dependence in Public Sector Healthcare: Benefits and Barriers.

    Science.gov (United States)

    Duncan, Laura G; Mendoza, Sonia; Hansen, Helena

    Since its U.S. FDA approval in 2002, buprenorphine has been available for maintenance treatment of opiate dependence in primary care physicians' offices. Though buprenorphine was intended to facilitate access to treatment, disparities in utilization have emerged; while buprenorphine treatment is widely used in private care setting, public healthcare integration of buprenorphine lags behind. Through a review of the literature, we found that U.S. disparities are partly due to a shortage of certified prescribers, concern of patient diversion, as well as economic and institutional barriers. Disparity of buprenorphine treatment dissemination is concerning since buprenorphine treatment has specific characteristics that are especially suited for low-income patient population in public sector healthcare such as flexible dosing schedules, ease of concurrently treating co-morbidities such as HIV and hepatitis C, positive patient attitudes towards treatment, and the potential of reducing addiction treatment stigma. As the gap between buprenorphine treatment in public sector settings and private sector settings persists in the U.S., current research suggests ways to facilitate its dissemination.

  10. Recognizing Potential Buprenorphine Medication Misuse: Product Packaging Does Not Degrade With Laundering.

    Science.gov (United States)

    Gunderson, Erik W

    2015-01-01

    Expanded office-based buprenorphine opioid dependence treatment is associated with medication misuse and diversion consequences. Recurrent early refill requests may indicate misuse or diversion, although further research is needed on how to effectively recognize and address the issue in clinical practice. In the current study, patient report of damaged medication from laundering prompted evaluation of laundering on degradation of buprenorphine-containing product packages and contents. Four buprenorphine product packaging approaches were assessed: 3 buprenorphine/naloxone placebo demonstration products (Suboxone and Bunavail film in foil wrappers and Zubsolv tablet in a blister pack) and Rexam-manufactured Screw-Loc closure pill container filled with a chewable aspirin as a surrogate for generic buprenorphine and buprenorphine/naloxone products. Two experimental laundering conditions, wash machine alone (W) and washer/dryer (W+D), were compared with unlaundered control (C) condition. Standard laundering settings were based on patient presentation. Products from the 2 experimental conditions and the control condition were labeled A, B, or C with counterbalanced assignment prior to visual examination of packaging and contents by the investigator who was blinded to condition. Packaging and contents remained intact for all products across experimental conditions, with only minor cosmetic effects compared with control. The W+D Suboxone film had 1-2 mm curling of the wrapper corners. Zubsolv blister packs had slight paper label fading (W+D > W). Bunavail W+D foil had an indentation outlining the inner film. The W+D bottle tablet had a ˜1 mm nick on one edge. No other differences were noted. After implementing more structured treatment and reviewing the results with the patient, he endorsed fabricating the laundering story to get additional medication. Laundering is an unlikely cause of damaged buprenorphine-containing medication packaged in foil wrappers (Suboxone

  11. Pharmacokinetics of buprenorphine hydrochloride following intramuscular and intravenous administration to American kestrels (Falco sparverius).

    Science.gov (United States)

    Gustavsen, Kate A; Guzman, David Sanchez-Migallon; Knych, Heather K; Petritz, Olivia A; Olsen, Glenn H; Paul-Murphy, Joanne R

    2014-08-01

    To determine the pharmacokinetics of buprenorphine hydrochloride after IM and IV administration to American kestrels (Falco sparverius). 13 healthy 3-year-old captive-bred American kestrels. Buprenorphine hydrochloride (0.6 mg/kg) was administered IM to all birds. Blood samples were collected at 9 times, ranging from 5 minutes to 9 hours after drug administration. Plasma buprenorphine concentrations were measured by use of tandem liquid chromatography-mass spectrometry. Pharmacokinetic parameters were determined by use of least squares linear regression and noncompartmental analysis of naïve pooled data. After a washout period of 2 weeks, the same dose of buprenorphine was administered IV to all birds and blood samples were collected at the same times after drug administration. Maximum plasma buprenorphine concentration was achieved within 5 minutes after IM administration. For IM administration, bioavailability was 94.8% and elimination half-life was 92.1 minutes. For IV administration, steady-state volume of distribution was 4,023.8 mL/kg, plasma clearance was 49.2 mL/min/kg, and elimination half-life was 105.5 minutes. Buprenorphine was rapidly absorbed, and bioavailability was good after IM administration to American kestrels. Plasma buprenorphine concentrations were > 1 ng/mL for 9 hours after both IM and IV administration. These results, in combination with those of a pharmacodynamic study, suggested that the analgesic effects of buprenorphine could last at least 6 to 9 hours in this species. Further investigations of the duration of analgesic effects, multiple-dose protocols, and potential adverse effects of buprenorphine are warranted in American kestrels and other raptors.

  12. Buprenorphine and methadone for opioid addiction during pregnancy.

    Science.gov (United States)

    Mozurkewich, Ellen L; Rayburn, William F

    2014-06-01

    Buprenorphine and methadone are opioid-receptor agonists used as opioid substitution therapy during pregnancy to limit exposure of the fetus to cycles of opioid withdrawal and reduce the risk of infectious comorbidities of illicit opioid use. As part of a comprehensive care plan, such therapy may result in improved access to prenatal care, reduced illicit drug use, reduced exposure to infections associated with intravenous drug use, and improved maternal nutrition and infant birth weight. This article describes differences in patient selection between the two drugs, their relative safety during pregnancy, and changes in daily doses as a guide for prescribing clinicians. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Subcutaneous Implants of Buprenorphine-Cholesterol-Triglyceride Powder in Mice

    OpenAIRE

    L. DeTolla; R. Sanchez; E. Khan; B. Tyler; M. Guarnieri

    2014-01-01

    Subcutaneous drug implants are convenient systems for the long-term delivery of drugs in animals. Lipid carriers are logical tools because they generally allow for higher doses and low toxicity. The present study used an US Food and Drug Administration Target Animal Safety test system to evaluate the safety of a subcutaneous implant of a cholesterol-triglyceride-buprenorphine powder in 120 BALB/c mice. Mice were evaluated in 4- and 12-day trials with 1- and 5-fold doses of the intended 3 mg/k...

  14. Effects of Time and Storage Conditions on the Chemical and Microbiologic Stability of Diluted Buprenorphine for Injection.

    Science.gov (United States)

    DenHerder, Johnathan M; Reed, Ralph L; Sargent, Jennifer L; Bobe, Gerd; Stevens, Jan F; Diggs, Helen E

    2017-07-01

    Buprenorphine is a partial μ-opioid agonist used for analgesia. Due to the small size of laboratory rodents, buprenorphine HCl is typically diluted 10- or 20-fold with a sterile diluent, such as saline, for accurate dosing. Protocols for preparing and storing diluted buprenorphine vary by institution, and little published information is available regarding stability and beyond-use dating of specific buprenorphine preparations. The purpose of this study was to determine the chemical and microbiologic stability of diluted buprenorphine stored for a maximum of 180 d. Buprenorphine HCl was diluted 1:10 into sterile bacteriostatic saline by using aseptic technique. Diluted samples were stored in glass vials or plastic syringes, protected from light, and maintained at refrigerated or room temperature for as long as 180 d. Aerobic and anaerobic cultures on all stored samples were negative for bacterial and fungal growth. According to HPLC analysis, diluted buprenorphine stored in glass vials experienced less than 10% loss when stored for 180 d at either refrigerated or room temperature. However, the concentration of buprenorphine stored in syringes declined rapidly to more than 80% loss at room temperature and 28% loss in the refrigerator after 180 d. According to the results of this study, diluted buprenorphine stored in glass vials retains more than 90% of the initial concentration and is microbiologically stable for 180 d. However, our data suggest that, regardless of the duration, storing diluted buprenorphine in plastic syringes is inadvisable.

  15. A successful treatment of buprenorphine withdrawal with the dopamine receptor agonist pramipexole.

    Science.gov (United States)

    Makhinson, Michael; Gomez-Makhinson, Juliana

    2014-01-01

    Buprenorphine, used for treating opioid dependence, may have a withdrawal syndrome requiring treatment. Modulation of the dopamine system, which has been implicated in opioid withdrawal, may be a target for withdrawal for opioids such as buprenorphine. A case is reported of a buprenorphine withdrawal syndrome with predominant symptoms of restlessness that were resistant to clonidine and benzodiazepines. It was successfully treated with the dopamine agonist pramipexole. Dopamine receptor agonists may have a place in the treatment of restlessness associated with opioid withdrawal and may have value for the broader spectrum of opioid withdrawal symptoms. © American Academy of Addiction Psychiatry.

  16. Pharmacokinetics of buprenorphine in a sodium carboxymethylcellulose gel after buccal transmucosal administration in dogs.

    Science.gov (United States)

    Krotscheck, Ursula; Boothe, Dawn Merton; Little, Amy A; Erb, Hollis N

    2010-01-01

    Alternatives to intravenous administration of opioids are needed in veterinary medicine. Previous research suggests that opioids can be administered through the buccal mucosa in dogs. This study reports the pharmacokinetics of buprenorphine HCl (0.05 mg/kg) administered transmucosally in six dogs compared with those of buprenorphine HCl (0.015 mg/kg) administered intravenously. The results suggest that the pharmacokinetics of buprenorphine HCl administered intravenously or transmucosally are similar and that transmucosal administration may be considered as a noninvasive alternative to intravenous administration.

  17. Pharmacokinetics of 2 Formulations of Buprenorphine in Macaques (Macaca mulatta and Macaca fascicularis)

    Science.gov (United States)

    Nunamaker, Elizabeth A; Halliday, Lisa C; Moody, David E; Fang, Wenfang B; Lindeblad, Matthew; Fortman, Jeffrey D

    2013-01-01

    Buprenorphine is the cornerstone of pain management in nonhuman primates, but the pharmacokinetics of this widely used drug are unknown. The purpose of this study was to evaluate the pharmacokinetic profiles of buprenorphine (0.01 and 0.03 mg/kg IM) and sustained-release buprenorphine (0.2 mg/kg SC) in 2 macaque species (M. mulatta and M. fascicularis) by using mass spectrometry. The pharmacokinetics did not differ significantly between species, and buprenorphine was dose-proportional at the tested doses. The low and high doses of buprenorphine had elimination half-lives of 2.6 ± 0.7 and 5.3 ± 2.0 h, respectively, but the low-dose data were constrained by the sensitivity of the analytical method. Sustained-release buprenorphine had an elimination half-life of 42.6 ± 26.2 h. The AUC0-Tlast of buprenorphine were 9.1 ± 4.3 and 39.0 ± 25.1 ng×h/mL for the low and high doses, respectively, and sustained-release buprenorphine had an AUC0-Tlast of 177 ± 74 ng×h/mL. Assuming a hypothesized therapeutic buprenorphine plasma concentration threshold of 0.1 ng/mL in macaques, these results suggest that buprenorphine doses of 0.01 mg/kg IM should be administered every 6 to 8 h, whereas doses of 0.03 mg/kg IM can be administered every 12 h. These results further demonstrate that a single 0.2-mg/kg SC injection of sustained-release buprenorphine maintains plasma concentrations above 0.1 ng/mL for 5 d in macaques. These findings support a new dosing strategy using sustained-release buprenorphine to improve pain management, decrease animal stress, improve animal welfare, and simplify the postoperative management of nonhuman primates in laboratory animal and zoological settings. PMID:23562033

  18. Intravenous use of illicit buprenorphine/naloxone to reverse an acute heroin overdose.

    Science.gov (United States)

    Yokell, Michael A; Zaller, Nickolas D; Green, Traci C; McKenzie, Michelle; Rich, Josiah D

    2012-01-01

    A case of heroin overdose reversed through the intravenous (IV) administration of a crushed sublingual tablet of buprenorphine/naloxone (Suboxone) by a lay responder is described. Although the sublingual administration of buprenorphine/naloxone to reverse an overdose has been reported elsewhere, this is the first report of IV administration. Healthcare professionals should be aware that injection drug users may respond to an opioid overdose by injecting buprenorphine/naloxone and should consequently counsel all opioid-using patients on the proper response to an overdose. Physicians should also consider prescribing naloxone to at-risk patients. The work of community-based naloxone distribution programs should be expanded.

  19. Overlapping buprenorphine, opioid, and benzodiazepine prescriptions among veterans dually enrolled in Department of Veterans Affairs and Medicare Part D.

    Science.gov (United States)

    Gellad, Walid F; Zhao, Xinhua; Thorpe, Carolyn T; Thorpe, Joshua M; Sileanu, Florentina E; Cashy, John P; Mor, Maria; Hale, Jennifer A; Radomski, Thomas; Hausmann, Leslie R M; Fine, Michael J; Good, Chester B

    2017-01-01

    Buprenorphine is a key tool in the management of opioid use disorder, but there are growing concerns about abuse, diversion, and safety. These concerns are amplified for the Department of Veterans Affairs (VA), whose patients may receive care concurrently from multiple prescribers within and outside VA. To illustrate the extent of this challenge, we examined overlapping prescriptions for buprenorphine, opioids, and benzodiazepines among veterans dually enrolled in VA and Medicare Part D. We constructed a cohort of all veterans dually enrolled in VA and Part D who filled an opioid prescription in 2012. We identified patients who received tablet or film buprenorphine products from either source. We calculated the proportion of buprenorphine recipients with any overlapping prescription (based on days supply) for a nonbuprenorphine opioid or benzodiazepine, focusing on veterans who received overlapping prescriptions from a different system than their buprenorphine prescription (Part D buprenorphine recipients receiving overlapping opioids or benzodiazepines from VA and vice versa). There were 1790 dually enrolled veterans with buprenorphine prescriptions, including 760 (43%) from VA and 1091 (61%) from Part D (61 veterans with buprenorphine from both systems were included in each group). Among VA buprenorphine recipients, 199 (26%) received an overlapping opioid prescription and 11 (1%) received an overlapping benzodiazepine prescription from Part D. Among Part D buprenorphine recipients, 208 (19%) received an overlapping opioid prescription and 178 (16%) received an overlapping benzodiazepine prescription from VA. Among VA and Part D buprenorphine recipients with cross-system opioid overlap, 25% (49/199) and 35% (72/208), respectively, had >90 days of overlap. Many buprenorphine recipients receive overlapping prescriptions for opioids and benzodiazepines from a different health care system than the one in which their buprenorphine was filled. These findings highlight

  20. Intranasal buprenorphine alone and in combination with naloxone: Abuse liability and reinforcing efficacy in physically dependent opioid abusers.

    Science.gov (United States)

    Walsh, Sharon L; Nuzzo, Paul A; Babalonis, Shanna; Casselton, Victoria; Lofwall, Michelle R

    2016-05-01

    Buprenorphine can be abused by the intranasal route. This study sought to examine the relative abuse liability and reinforcing efficacy of intranasal buprenorphine compared to intranasal buprenorphine/naloxone in opioid-dependent individuals. Eleven healthy male and female volunteers physically dependent on short-acting opioids resided as inpatients during participation in this double blind, within subject, placebo-controlled study. Participants were maintained on oxycodone (30 mg/q.i.d., p.o.) throughout the 6-week study. Eight pairs of experimental sessions were conducted at ≥48 h intervals to examine the pharmacodynamic profile (Sample) and reinforcing efficacy (Self-administration the following day) of intranasal placebo, oxycodone (60 mg), buprenorphine (2, 8 & 16 mg) and buprenorphine/naloxone (2/0.5, 8/2 & 16/4 mg). Subjective, observer-rated and physiological measures were collected to assess the magnitude of opioid agonist and antagonist effects. A progressive ratio self-administration procedure assessed choices for drug versus money. All active doses produced opioid agonist-like effects (e.g., increased ratings of "liking," and miosis) compared to placebo. The effects of buprenorphine and buprenorphine/naloxone were not reliably dose-dependent. Intranasal buprenorphine/naloxone elicited modest and transient opioid withdrawal-like effects in the first hour post-drug administration, while simultaneously blunting or blocking the early onset of agonist effects seen with buprenorphine alone. All active doses of buprenorphine were self-administered more than placebo, but buprenorphine/naloxone doses were not. These data confirm that intranasal buprenorphine/naloxone has deterrent properties related to transient withdrawal effects that likely decrease its desirability for misuse compared to buprenorphine in opioid-dependent individuals maintained on short-acting opioids. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Comparison of the efficacy and adverse effects of sustained-release buprenorphine hydrochloride following subcutaneous administration and buprenorphine hydrochloride following oral transmucosal administration in cats undergoing ovariohysterectomy.

    Science.gov (United States)

    Catbagan, Davina L; Quimby, Jessica M; Mama, Khursheed R; Rychel, Jessica K; Mich, Patrice M

    2011-04-01

    To compare the efficacy and adverse effects of sustained-release (SR) buprenorphine following SC administration and buprenorphine following oral transmucosal (OTM) administration in cats undergoing ovariohysterectomy. Animals-21 young healthy female cats. As part of anesthetic premedication (0 hours), 10 cats received buprenorphine (0.02 mg/kg) via OTM administration with additional doses at 12, 24, 36, 48, and 60 hours and 11 cats received an equivalent total dose as a single SC injection of SR buprenorphine (0.12 mg/kg). The SR product contained buprenorphine hydrochloride in a proprietary SR matrix. All other anesthetic drugs and a single postoperative dose of meloxicam were administered similarly to all cats. Behavioral and physiologic variables were recorded, and signs of pain were assessed by use of 2 pain assessment scales and von Frey filament testing in each cat prior to premedication administration (baseline), during recovery from anesthesia (RFA), and at 12, 24, 36, 48, 60, and 72 hours. Heart rate increased and temperature (determined via microchip transponder thermometry) decreased from baseline values during RFA in both groups. Compared with baseline values, pain scores were increased during RFA and at the 12- and 24-hour time points in both groups; von Frey scores were higher during RFA. Behavioral and physiologic variables did not differ significantly between groups at any time point. In cats undergoing ovariohysterectomy, SC administration of a preoperative dose of SR buprenorphine appeared to have comparable efficacy and adverse effect profile as that of twice-daily OTM administration of buprenorphine before and after surgery.

  2. Buprenorphine+Naloxone plus Naltrexone for the Treatment of Cocaine Dependence: The Cocaine Use Reduction with Buprenorphine (CURB) Study

    Science.gov (United States)

    Ling, Walter; Hillhouse, Maureen P.; Saxon, Andrew J.; Mooney, Larissa J.; Thomas, Christie M.; Ang, Alfonso; Matthews, Abigail G.; Hasson, Albert; Annon, Jeffrey; Sparenborg, Steve; Liu, David S.; McCormack, Jennifer; Church, Sarah; Swafford, William; Drexler, Karen; Schuman, Carolyn; Ross, Stephen; Wiest, Katharina; Korthuis, P. Todd; Lawson, William; Brigham, Gregory S.; Knox, Patricia C.; Dawes, Michael; Rotrosen, John

    2016-01-01

    Aims To examine the safety and effectiveness of buprenorphine+naloxone sublingual tablets (BUP, as Suboxone®) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Methods This multi-centered, double-blind, placebo-controlled study, conducted under the auspices of the National Drug Abuse Treatment Clinical Trials Network, randomly assigned 302 participants at sites in California, Oregon, Washington, Colorado, Texas, Georgia, Ohio, New York, and Washington D.C., USA to 1 of 3 conditions provided with XR-NTX: 4mg/day BUP (BUP4, n=100), 16mg/day BUP (BUP16, n=100), or no buprenorphine (placebo; PLB, n=102). Participants received pharmacotherapy for 8 weeks, with 3 clinic visits per week. Cognitive Behavioral Therapy was provided weekly. Follow-up assessments occurred at 1 and 3 months post-intervention. The planned primary outcome was urine drug screen (UDS)-corrected, self-reported cocaine use during the last 4 weeks of treatment. Planned secondary analyses assessed cocaine use by UDS, medication adherence, retention, and adverse events. Results No group differences were found between groups for the primary outcome (BUP4 vs. PLB, p=0.262; BUP16 vs PLB, p=0.185). Longitudinal analysis of UDS data during the evaluation period using generalized linear mixed equations found a statistically significant difference between BUP16 and PLB (p=0.022, OR=1.71) but not for BUP4 (p=0.105, OR=1.05). No secondary outcome differences across groups were found for adherence, retention, or adverse events. Conclusions Buprenorphine+naloxone, used in combination with naltrexone, may be associated with reductions in cocaine use among people who meet DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. PMID:26948856

  3. Dose-related antinociceptive effects of intravenous buprenorphine in cats.

    Science.gov (United States)

    Steagall, Paulo V M; Mantovani, Fernanda B; Taylor, Polly M; Dixon, Mike J; Luna, Stelio P L

    2009-11-01

    The dose-related antinociceptive effects of intravenous (IV) buprenorphine were evaluated in cats. Thermal (TT) and mechanical threshold (MT) devices were used for nociceptive stimulation. After baseline threshold recordings, buprenorphine was administered IV (0.01, 0.02 or 0.04 mg/kg; B1, B2 and B4, respectively) in a randomised, blinded and cross-over study. Data were analysed by ANOVA (P<0.05) using 95% confidence intervals (CI). TT increased 15, 30, 45 min and 1 (5.2+/-2.7 degrees C), 2, 3 and 4 h after B1; 15, 30, 45 min and 1 (5.1+/-3.9 degrees C) and 2 h after B2, and 15, 30, 45 min and 1 (5.4+/-3.3 degrees C), 2, 3, 6 and 8 h after B4. MT increased 15 and 45 min after B2 (260+/-171 mmHg), and 30 (209+/-116 mmHg) and 45 min and 1 and 2 h after B4. At 45 min, MT values were significantly higher after B2 compared to B1 (P<0.05). With MT, B2 and B4 produced more antinociception and longer duration of action than B1, respectively. No dose response to thermal stimulation was detected.

  4. Buprenorphine vs methadone treatment: A review of evidence in both developed and developing worlds

    Directory of Open Access Journals (Sweden)

    Paul J Whelan

    2012-01-01

    Full Text Available Heroin dependence is a major health and social problem associated with increased morbidity and mortality that adversely affects social circumstances, productivity, and healthcare and law enforcement costs. In the UK and many other Western countries, both methadone and buprenorphine are recommended by the relevant agencies for detoxification from heroin and for opioid maintenance therapy. However, despite obvious benefits due to its unique pharmacotherapy (eg, greatly reduced risk of overdose, buprenorphine has largely failed to overtake methadone in managing opioid addiction. The experience from the developing world (based on data from India is similar. In this article we compare the advantages and disadvantages of the use methadone and buprenorphine for the treatment of opioid addiction from both a developed and developing world perspective; and explore some of the reasons why buprenorphine has not fulfilled the expectations predicted by many in the addictions field.

  5. Pharmacokinetics of buprenorphine following intravenous and oral transmucosal administration in dogs.

    Science.gov (United States)

    Abbo, Lisa A; Ko, Jeff C H; Maxwell, Lara K; Galinsky, Raymond E; Moody, David E; Johnson, Brenda M; Fang, Wenfang B

    2008-01-01

    Pharmacokinetic analysis of buprenorphine administered to six healthy dogs via the oral transmucosal (OTM) route at doses of 20 and 120 microg/kg was conducted using liquid chromatography-electrospray ionization-tandem mass spectroscopy (LC-ESI-MS/MS). Bioavailability was 38% plus or minus 12% for the 20 microg/kg dose and 47%+/-16% for the 120 microg/kg dose. Maximum plasma concentrations were similar for buprenorphine doses of 20 microg/kg IV and 120 microg/kg OTM. Sedation and salivation were common side effects, but no bradycardia, apnea, or cardiorespiratory depressive effects were seen. When the two OTM dosing rates were normalized to dose, LC-ESI-MS/MS analysis of buprenorphine and its metabolites detected no significant difference (P>.05), indicating dose proportionality. The results of this study suggest that OTM buprenorphine may be an alternative for pain management in dogs.

  6. Assessment of the sedative effects of buprenorphine administered with 20 microg/kg detomidine in horses.

    Science.gov (United States)

    Love, E J; Taylor, P M; Murrell, J; Whay, H R; Waterman-Pearson, A E

    2011-04-16

    The aim of this randomised, observer-blinded, crossover study was to compare the effects of four treatments, administered intravenously to six horses: saline and saline; 10 µg/kg detomidine and 7.5 µg/kg buprenorphine; 20 µg/kg detomidine and 7.5 µg/kg buprenorphine; and 20 µg/kg detomidine and 10 µg/kg buprenorphine. Sedation was subjectively assessed and recorded on a visual analogue scale. Peak sedation and duration of sedation were investigated using a univariate general linear model with post-hoc Tukey tests (Pbuprenorphine (7.5 µg/kg). When administered with 20 µg/kg detomidine, increasing the dose of buprenorphine from 7.5 to 10 µg/kg did not influence the degree of sedation achieved.

  7. Adoption of Evidence-Based Clinical Innovations: The Case of Buprenorphine Use by Opioid Treatment Programs

    Science.gov (United States)

    Andrews, Christina M.; D’Aunno, Thomas A.; Pollack, Harold A.; Friedmann, Peter D.

    2015-01-01

    This article examines changes from 2005 to 2011 in the use of an evidence-based clinical innovation, buprenorphine use, among a nationally representative sample of opioid treatment programs and identifies characteristics associated with its adoption. We apply a model of the adoption of clinical innovations that focuses on the work needs and characteristics of staff; organizations’ technical and social support for the innovation; local market dynamics and competition; and state policies governing the innovation. Results indicate that buprenorphine use increased 24% for detoxification and 47% for maintenance therapy between 2005 and 2011. Buprenorphine use was positively related to reliance on private insurance and availability of state subsidies to cover its cost and inversely related to the percentage of clients who injected opiates, county size, and local availability of methadone. The results indicate that financial incentives and market factors play important roles in opioid treatment programs’ decisions to adopt evidence-based clinical innovations such as buprenorphine use. PMID:24051897

  8. Antinociceptive effects of voluntarily ingested buprenorphine in the hot-plate test in laboratory rats

    DEFF Research Database (Denmark)

    Kristensen, Sara Hestehave; Munro, Gordon; Brønnum Pedersen, Tina

    2017-01-01

    . In addition, it is desirable to provide post-operative analgesia using methods that are minimally invasive and stressful. This study investigated the antinociceptive effects of orally administered buprenorphine ingested in Nutella® in comparison with subcutaneous buprenorphine administration. By exposing...... the animal to a thermal stimulus using a hot plate, significant antinociceptive effects of voluntarily ingested buprenorphine administered in Nutella® were demonstrated. This was evident at doses of 1.0 mg/kg 60 and 120 min post administration (P... as with subcutaneous administration, and had a later onset. It is advised to administer the oral formulation of buprenorphine in Nutella® in a 10-fold higher dose, as well as approximately 60 min earlier, than with the more commonly employed subcutaneous route of administration....

  9. Buprenorphine shared medical appointments for the treatment of opioid dependence in a homeless clinic.

    Science.gov (United States)

    Doorley, Sara L; Ho, Cheryl J; Echeverria, Elizabeth; Preston, Charles; Ngo, Huy; Kamal, Ahmad; Cunningham, Chinazo O

    2017-01-01

    Opioid misuse and dependence are prevalent and rising problems in the United States. Treatment with buprenorphine is a successful treatment option for individuals with opioid dependence. This study describes and preliminarily evaluates a unique delivery system that provides buprenorphine treatment via a shared medical appointment. A retrospective medical record review on all 77 opioid-dependent patients referred for a buprenorphine shared medical appointment in a homeless clinic from 2010 to 2012. Most patients were currently homeless (61%), unemployed (92%), had an Axis I psychiatric diagnosis (81%), and had recent polysubstance use (53%). Of the 77 patients, 95% attended at least 1 shared medical appointment. Treatment retention at 12 and 24 weeks was 86% and 70%, respectively. In a patient population with complex social and mental health histories, buprenorphine treatment via a shared medical appointment had high retention rates. Findings can help guide the development of unique delivery systems to serve real-world complex patients with opioid dependence.

  10. Buprenorphine prescribing practices and exposures reported to a poison center--Utah, 2002-2011.

    Science.gov (United States)

    2012-12-14

    Buprenorphine is an effective medication for the treatment of opioid dependence. Its use has increased in the United States as a result of the Drug Addiction Treatment Act of 2000, which allowed physicians to prescribe certain medications as part of office-based treatment for opioid addiction. In France, widespread use of medication-assisted therapy, primarily buprenorphine treatment, was associated with an 80% decrease in overdose deaths from heroin or cocaine from 465 in 1996 to 89 in 2003. With the expanded use of buprenorphine, an increase in exposures among children and adults has been reported in the United States. These exposures (including unintentional and intentional, therapeutic and nontherapeutic) have resulted in adverse effects and, in a small number of cases, death. To assess statewide increases in buprenorphine use and the number of reported exposures, the Utah Department of Health analyzed data from the Utah Controlled Substance Database (CSD) and the Utah Poison Control Center (PCC). The results of that analysis indicated a statewide increase in the annual number of patients prescribed buprenorphine from 22 in 2002 to 9,793 in 2011, and a concurrent increase in the annual number of prescribers writing buprenorphine prescriptions from 16 to 1,088. Over the same period, the number of exposures to buprenorphine reported annually to the PCC increased from six to 81. However, comparison of the ratios of buprenorphine exposures to patients and prescribers in 2002 with data for 2011 indicated substantial decreases from 6/22 for patients and 6/16 for prescribers in 2002 to 81/9,793 for patients and 81/1,088 for prescribers in 2011. Three of the total 462 buprenorphine exposures reported during 2002-2011 in Utah, in a teen and two adults, were associated with fatal outcomes. Increased buprenorphine prescribing in Utah during 2002-2011 likely represents expanded access to critically needed opioid addiction treatment; however, safeguards should be in place

  11. Primary care management of opioid use disorders: Abstinence, methadone, or buprenorphine-naloxone?

    Science.gov (United States)

    Srivastava, Anita; Kahan, Meldon; Nader, Maya

    2017-03-01

    To advise physicians on which treatment options to recommend for specific patient populations: abstinence-based treatment, buprenorphine-naloxone maintenance, or methadone maintenance. PubMed was searched and literature was reviewed on the effectiveness, safety, and side effect profiles of abstinence-based treatment, buprenorphine-naloxone treatment, and methadone treatment. Both observational and interventional studies were included. Both methadone and buprenorphine-naloxone are substantially more effective than abstinence-based treatment. Methadone has higher treatment retention rates than buprenorphine-naloxone does, while buprenorphine-naloxone has a lower risk of overdose. For all patient groups, physicians should recommend methadone or buprenorphine-naloxone treatment over abstinence-based treatment (level I evidence). Methadone is preferred over buprenorphine-naloxone for patients at higher risk of treatment dropout, such as injection opioid users (level I evidence). Youth and pregnant women who inject opioids should also receive methadone first (level III evidence). If buprenorphine-naloxone is prescribed first, the patient should be promptly switched to methadone if withdrawal symptoms, cravings, or opioid use persist despite an optimal buprenorphine-naloxone dose (level II evidence). Buprenorphine-naloxone is recommended for socially stable prescription oral opioid users, particularly if their work or family commitments make it difficult for them to attend the pharmacy daily, if they have a medical or psychiatric condition requiring regular primary care (level IV evidence), or if their jobs require higher levels of cognitive functioning or psychomotor performance (level III evidence). Buprenorphine-naloxone is also recommended for patients at high risk of methadone toxicity, such as the elderly, those taking high doses of benzodiazepines or other sedating drugs, heavy drinkers, those with a lower level of opioid tolerance, and those at high risk of

  12. No evidence of potentiation of buprenorphine by milnacipran in healthy subjects using a nociceptive test battery.

    Science.gov (United States)

    Okkerse, P; Alvarez-Jimenez, R; Hay, J L; Tehim, A; Kumar, R; de Kam, M L; Groeneveld, G J

    2017-03-01

    Serotonin-norepinephrine reuptake inhibitors inhibit the reuptake of serotonin and noradrenalin and are used in the treatment of neuropathic pain. Animal studies suggest that milnacipran co-administered with opioids may potentiate the analgesic effect of μ-opioid receptor agonists. This study hypothesized that co-administration of milnacipran and buprenorphine would have a synergistic effect in evoked pain models in healthy subjects. This was a randomized double-blinded, placebo-controlled, four-way cross-over, multiple dose clinical trial to investigate the analgesic effects of buprenorphine (placebo, 0.5, 1 and 3 μg/kg) in combination with milnacipran (placebo, 25 and 50 mg) in healthy subjects. 11 healthy men were enrolled in the study. Buprenorphine alone showed a dose-response relationship indicative of anti-nociception in the pain tests. Following milnacipran administration, no changes were seen in the pharmacodynamic measurements for pain, psychomotor function, body stability or eye movements. For the electrical tests, cold pressor test and pressure pain test, buprenorphine alone was superior when compared with buprenorphine plus milnacipran. No differences in pharmacodynamic variables, besides an increase in pupil/iris ratio, were observed after repeated administration of milnacipran 50 mg. Single and multiple doses of 25 or 50 mg milnacipran did not further potentiate the anti-nociceptive effects of buprenorphine. Buprenorphine showed dose-dependent effects consistent with its pharmacological profile. Milnacipran alone did not affect any of the pain variables. The combination of both buprenorphine and milnacipran did not potentiate or show a synergistic effect on the pain models used in this study. Buprenorphine is known to be a potent opioid agonist. Animal studies suggest that milnacipran co-administered with opioids may potentiate the analgesic effect of μ-opioid receptor agonists. Here, we found that buprenorphine showed a dose

  13. An evidence-based recommendation to increase the dosing frequency of buprenorphine during pregnancy.

    Science.gov (United States)

    Caritis, Steve N; Bastian, Jaime R; Zhang, Hongfei; Kalluri, Hari; English, Dennis; England, Michael; Bobby, Stephanie; Venkataramanan, Raman

    2017-10-01

    Dose-adjusted plasma concentrations of buprenorphine are significantly decreased during pregnancy compared with the nonpregnant state. This observation suggests that pregnant women may need a higher dose of buprenorphine than nonpregnant individuals to maintain similar drug exposure (plasma concentrations over time after a dose). The current dosing recommendations for buprenorphine during pregnancy address the total daily dose of buprenorphine to be administered, but the frequency of dosing is not clearly addressed. Based on buprenorphine's long terminal half-life, once-daily or twice-daily dosing has generally been suggested. The objective of the study was to assess the impact of dosing frequency on buprenorphine plasma concentration time course during pregnancy. We utilized 3 data sources to determine an optimal frequency for dosing of buprenorphine during pregnancy: data from a pharmacokinetic study of 14 pregnant and postpartum women on maintenance buprenorphine in a supervised clinical setting; data from pregnant women attending a buprenorphine clinic; and data from a physiologically based pharmacokinetic modeling of buprenorphine pharmacokinetics in nonpregnant subjects. Among the 14 women participating in the pharmacokinetic study during and after pregnancy, plasma concentrations of buprenorphine were <1 ng/mL (the theoretical concentration required to prevent withdrawal symptoms) for 50-80% of the 12 hour dosing interval while at steady state. Among 62 women followed up in a opioid agonist treatment program, in which dosing frequency is determined in part by patient preference, 10 (16%) were on once-daily dosing, 10 (16%) were on twice-daily dosing, 28 (45%) were on thrice-daily dosing, and 14 (23%) were on four-times-daily dosing. A physiologically based pharmacokinetic model in nonpregnant subjects demonstrated that dosing frequency has an impact on the duration over which the plasma concentrations are below a specified plasma concentration threshold. A

  14. Buprenorphine – an attractive opioid with underutilized potential in treatment of chronic pain

    OpenAIRE

    Pillarisetti, Sivaram; Khanna,Ish

    2015-01-01

    Ish K Khanna, Sivaram PillarisettiNeuroPn Therapeutics, Alpharetta, GA, USAAbstract: Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about “ceiling effect” or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed µ-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and n...

  15. Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers

    OpenAIRE

    Fischer, Andreas; J?nsson, Martin; Hjelmstr?m, Peter

    2013-01-01

    Abstract Context Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery. Objective To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability. Methods Dry mixing techniques were employed to produce a small and fast dissolving buprenorphine/naloxone sublingual tablet formulation, OX219 (Zubsolv?), using su...

  16. Evaluation of the perioperative analgesic efficacy of buprenorphine, compared with butorphanol, in cats.

    Science.gov (United States)

    Warne, Leon N; Beths, Thierry; Holm, Merete; Carter, Jennifer E; Bauquier, Sébastien H

    2014-07-15

    To compare the analgesic effects of buprenorphine and butorphanol in domestic cats. 2-phase positive-controlled randomized masked clinical trial. 39 healthy female cats (10 in phase 1 and 29 in phase 2). Cats admitted for ovariohysterectomy received buprenorphine (4 in phase 1; 14 in phase 2) or butorphanol (6 in phase 1; 15 in phase 2). In phase 1, cats were premedicated with buprenorphine (0.02 mg/kg [0.009 mg/lb], IM) or butorphanol (0.4 mg/kg [0.18 mg/lb], IM), in combination with medetomidine. Anesthesia was induced with propofol (IV) and maintained with isoflurane in oxygen. After extubation, medetomidine was antagonized with atipamezole. A validated multidimensional composite scale was used to assess signs of pain after surgery starting 20 minutes after extubation and continuing for up to 360 minutes, and pain score comparisons were made between the 2 groups. Phase 2 proceeded similar to phase 1 with the following addition: during wound closure, cats from the butorphanol and buprenorphine groups received butorphanol (0.4 mg/kg, IM) or buprenorphine (0.02 mg/kg, IM), respectively. Phase 1 of the study was stopped after 10 cats were ovariohysterectomized because 9 of 10 cats required rescue analgesia at the first evaluation. In phase 2, at the first pain evaluation, pain scores from the buprenorphine group were lower, and all cats from the butorphanol group required rescue analgesia. None of the cats from the buprenorphine group required rescue analgesia at any time. Buprenorphine (0.02 mg/kg, IM) given before surgery and during wound closure provided adequate analgesia for 6 hours following ovariohysterectomy in cats, whereas butorphanol did not.

  17. Budgetary impact analysis of buprenorphine-naloxone combination (Suboxone®) in Spain

    OpenAIRE

    Martinez-Raga, Jose; Gonzalez-Saiz, Francisco; Oñate, Julian; Oyagüez, Itziar; Sabater, Eliazar; A. Casado, Miguel

    2012-01-01

    Background: Opioid addiction is a worldwide problem. Agonist opioid treatment (AOT) is the most widespread and frequent pharmacotherapeutic approach. Methadone has been the most widely used AOT, but buprenorphine, a partial kappa-opiod agonist and a my-opiod antagonist, is fast gaining acceptance. The objective was to assess the budgetary impact in Spain of the introduction of buprenorphine-naloxone (B/N) combination. Methods: A budgetary impact model was developed to estimate healthcare cost...

  18. The Role of Behavioral Interventions in Buprenorphine Maintenance Treatment: A Review.

    Science.gov (United States)

    Carroll, Kathleen M; Weiss, Roger D

    2017-08-01

    Although counseling is a required part of office-based buprenorphine treatment of opioid use disorders, the nature of what constitutes appropriate counseling is unclear and controversial. The authors review the literature on the role, nature, and intensity of behavioral interventions in office-based buprenorphine treatment. The authors conducted a review of randomized controlled studies testing the efficacy of adding a behavioral intervention to buprenorphine maintenance treatment. Four key studies showed no benefit from adding a behavioral intervention to buprenorphine plus medical management, and four studies indicated some benefit for specific behavioral interventions, primarily contingency management. The authors examined the findings from the negative trials in the context of six questions: 1) Is buprenorphine that effective? 2) Is medical management that effective? 3) Are behavioral interventions that ineffective in this population? 4) How has research design affected the results of studies of buprenorphine plus behavioral treatment? 5) What do we know about subgroups of patients who do and those who do not seem to benefit from behavioral interventions? 6) What should clinicians aim for in terms of treatment outcome in buprenorphine maintenance? High-quality medical management may suffice for some patients, but there are few data regarding the types of individuals for whom medical management is sufficient. Physicians should consider a stepped-care model in which patients may begin with relatively nonintensive treatment, with increased intensity for patients who struggle early in treatment. Finally, with 6-month retention rates seldom exceeding 50% and poor outcomes following dropout, we must explore innovative strategies for enhancing retention in buprenorphine treatment.

  19. Effects of Buprenorphine, Methylnaltrexone, and Their Combination on Gastrointestinal Transit in Healthy New Zealand White Rabbits.

    Science.gov (United States)

    Martin-Flores, Manuel; Singh, Bhupinder; Walsh, Courtney A; Brooks, Elizabeth P; Taylor, Lacic; Mitchell, Lisa M

    2017-03-01

    Among the many analgesic agents available, buprenorphine appears to be the analgesic used most often in rabbits. Unfortunately, deleterious side effects of opioids, such as gastrointestinal stasis and anorexia, may discourage the use of these agents. Methylnaltrexone is a peripheral opioid antagonist that ameliorates opioid-induced gastrointestinal stasis in others species yet preserves the analgesic effects of buprenorphine. We evaluated whether methylnaltrexone reversed buprenorphine-induced gastrointestinal stasis in 8 healthy male New Zealand White rabbits. To measure gastrointestinal transit time, each rabbit received 20 barium-filled spheres through an orogastric tube. Rabbits then received 4 treatments in random order: buprenorphine (0.05 mg/kg SC), methylnaltrexone (1 mg/kg SC), both agents combined (B+M), or normal saline (control) every 12 h for 2 d. Fecal production was measured every 6 h, and water and food consumption, and body weight, were measured daily, for 5 d after each treatment. The time to appearance of the first sphere was significantly longer for buprenorphine group than for control and methylnaltrexone groups. Daily fecal output was lowest for buprenorphine and B+M, intermediate for control, and highest for methylnaltrexone. Water and food consumption were lower for groups buprenorphine and B+M than for control and methylnaltrexone. Body weight was not affected. In conclusion, treatment with buprenorphine 0.05 mg/kg BID for 2 d in healthy rabbits decreased food and water consumption, prolonged gastrointestinal transit time and decreased the fecal output. Coadministration of methylnaltrexone at 1 mg/kg did not alleviate these negative side effects.

  20. Text message content preferences to improve buprenorphine maintenance treatment in primary care.

    Science.gov (United States)

    Tofighi, Babak; Grossman, Ellie; Bereket, Sewit; D Lee, Joshua

    2016-01-01

    Few studies have evaluated text message content preferences to support evidence-based treatment approaches for opioid use disorders, and none in primary care office-based buprenorphine treatment settings. This study assessed the acceptability and preferences for a tailored text message intervention in support of core office-based buprenorphine treatment medical management components (e.g., treatment adherence, encouraging abstinence, 12-step group participation, motivational interviewing, and patient-provider communication as needed). There were 97 patients enrolled in a safety net office-based buprenorphine treatment program who completed a 24-item survey instrument that consisted of multiple-choice responses, 7-point Likert-type scales, binomial "Yes/No" questions, and open-ended responses. The sample was predominately male (81%), had an average age of 46 years, and was diverse (64% ethnic/racial minorities); 56% lacked stable employment. Respondents were interested in receiving text message appointment reminders (90%), information pertaining to their buprenorphine treatment (76%), supportive content (70%), and messages to reduce the risk of relapse (88%). Participants preferred to receive relapse prevention text messages during all phases of treatment: immediately after induction into buprenorphine treatment (81%), a "few months" into treatment (57%), and after discontinuing buprenorphine treatment (72%). Respondents also expressed interest in text message content enhancing self-efficacy, social support, and frequent provider communication to facilitate unobserved "home" induction with buprenorphine. Older participants were significantly less receptive to receiving text message appointment reminders; however, they were as interested in receiving supportive, informational, and relapse prevention components compared to younger respondents. Implications for integrating a text message support system in office-based buprenorphine treatment are discussed.

  1. Treatment Outcomes of African American Buprenorphine Patients by Parole and Probation Status

    OpenAIRE

    Mitchell, Shannon Gwin; Gryczynski, Jan; Kelly, Sharon M.; O’Grady, Kevin E.; Jaffe, Jerome H.; Olsen, Yngvild K.; Schwartz, Robert P.

    2014-01-01

    This secondary analysis compared outcomes of African-American adults newly-admitted to buprenorphine treatment who were on parole and probation to patients who were not under criminal justice supervision. Buprenorphine patients (N=300) were randomly assigned to receive either Intensive Outpatient Treatment (IOP) or Standard Outpatient Treatment (OP) treatment and were assessed at baseline, 3- and 6-months. There were no differences between groups in treatment retention. Among probationers/par...

  2. The relative risk of fatal poisoning by methadone or buprenorphine within the wider population of England and Wales.

    Science.gov (United States)

    Marteau, Dave; McDonald, Rebecca; Patel, Kamlesh

    2015-05-29

    To examine the population-wide overdose risk emerging from the prescription of methadone and buprenorphine for opioid substitution treatment in England and Wales. Retrospective administrative data study. National databases for England and Wales. Drug-related mortality data were drawn from the Office for National Statistics, and prescription data for methadone and buprenorphine were obtained from the National Health Service for the years 2007-2012. During this 6-year period, a total of 2366 methadone-related deaths and 52 buprenorphine-related deaths were registered, corresponding to 17,333,163 methadone and 2,602,374 buprenorphine prescriptions issued. The analysis encompassed poisoning deaths among members of the wider population of England and Wales who consumed, but were not prescribed these medications, in addition to patients prescribed methadone or buprenorphine. Mortality risk: substance-specific overdose rate per 1000 prescriptions issued; relative risk ratio of methadone in relation to buprenorphine. During the years 2007-2012, the pooled overdose death rate was 0.137/1000 prescriptions of methadone, compared to 0.022/1000 prescriptions of buprenorphine (including buprenorphine-naloxone). The analysis generated a relative risk ratio of 6.23 (95% CI 4.79 to 8.10) of methadone in relation to buprenorphine. UK Borders Agency data were taken into consideration and revealed that only negligible amounts of methadone and buprenorphine were seized on entering UK territory between 2007 and 2012, suggesting domestic diversion. Our analysis of the relative safety of buprenorphine and methadone for opioid substitution treatment reveals that buprenorphine is six times safer than methadone with regard to overdose risk among the general population. Clinicians should be aware of the increased risk of prescribing methadone, and tighter regulations are needed to prevent its diversion. Published by the BMJ Publishing Group Limited. For permission to use (where not already

  3. Buprenorphine Disrupts Sleep and Decreases Adenosine Levels in Sleep-Regulating Brain Regions of Sprague Dawley Rat

    Science.gov (United States)

    Gauthier, Elizabeth A.; Guzick, Sarah E.; Brummett, Chad M.; Baghdoyan, Helen A.; Lydic, Ralph

    2011-01-01

    Background Buprenorphine, a partial μ opioid receptor agonist and κ opioid receptor antagonist, is an effective analgesic. The effects of buprenorphine on sleep have not been well characterized. This study tested the hypothesis that an antinociceptive dose of buprenorphine decreases sleep and decreases adenosine levels in regions of the basal forebrain and pontine brain stem that regulate sleep. Methods Male Sprague Dawley rats were implanted with intravenous catheters and electrodes for recording states of wakefulness and sleep. Buprenorphine (1 mg/kg) was administered systemically via an indwelling catheter and sleep/wake states were recorded for 24 h. In additional rats buprenorphine was delivered by microdialysis to the pontine reticular formation and substantia innominata of the basal forebrain while simultaneously measuring adenosine. Results An antinociceptive dose of buprenorphine caused a significant increase in wakefulness (25.2%) and a decrease in both nonrapid eye movement sleep (−22.1%) and rapid eye movement sleep (−3.1%). Buprenorphine also increased electroencephalographic delta power during nonrapid eye movement sleep. Coadministration of the sedative/hypnotic eszopiclone diminished the buprenorphine-induced decrease in sleep. Dialysis delivery of buprenorphine significantly decreased adenosine levels in the pontine reticular formation (−14.6%) and substantia innominata (−36.7%). Intravenous administration of buprenorphine significantly decreased (−20%) adenosine in the substantia innominata. Conclusions Buprenorphine significantly increased time spent awake, decreased nonrapid eye movement sleep, and increased latency to sleep onset. These disruptions in sleep architecture were mitigated by coadministration of the nonbenzodiazepine sedative/hypnotic eszopiclone. The buprenorphine-induced decrease in adenosine levels in basal forebrain and pontine reticular formation is consistent with the interpretation that decreasing adenosine in

  4. The relative risk of fatal poisoning by methadone or buprenorphine within the wider population of England and Wales

    Science.gov (United States)

    Marteau, Dave

    2015-01-01

    Objective To examine the population-wide overdose risk emerging from the prescription of methadone and buprenorphine for opioid substitution treatment in England and Wales. Design Retrospective administrative data study. Setting National databases for England and Wales. Participants/cases Drug-related mortality data were drawn from the Office for National Statistics, and prescription data for methadone and buprenorphine were obtained from the National Health Service for the years 2007–2012. During this 6-year period, a total of 2366 methadone-related deaths and 52 buprenorphine-related deaths were registered, corresponding to 17 333 163 methadone and 2 602 374 buprenorphine prescriptions issued. The analysis encompassed poisoning deaths among members of the wider population of England and Wales who consumed, but were not prescribed these medications, in addition to patients prescribed methadone or buprenorphine. Main outcome measures Mortality risk: substance-specific overdose rate per 1000 prescriptions issued; relative risk ratio of methadone in relation to buprenorphine. Results During the years 2007–2012, the pooled overdose death rate was 0.137/1000 prescriptions of methadone, compared to 0.022/1000 prescriptions of buprenorphine (including buprenorphine-naloxone). The analysis generated a relative risk ratio of 6.23 (95% CI 4.79 to 8.10) of methadone in relation to buprenorphine. UK Borders Agency data were taken into consideration and revealed that only negligible amounts of methadone and buprenorphine were seized on entering UK territory between 2007 and 2012, suggesting domestic diversion. Conclusions Our analysis of the relative safety of buprenorphine and methadone for opioid substitution treatment reveals that buprenorphine is six times safer than methadone with regard to overdose risk among the general population. Clinicians should be aware of the increased risk of prescribing methadone, and tighter regulations are needed to prevent its

  5. Effect of buprenorphine on the cardiovascular and respiratory response to visceral pain in conscious rabbits.

    Science.gov (United States)

    Shafford, Heidi L; Schadt, James C

    2008-07-01

    To evaluate the effect of buprenorphine administration on the cardiovascular and respiratory responses to noxious colorectal distension in conscious rabbits. Prospective experimental trial. Fifteen healthy, young adult New Zealand white rabbits (eight female). Experiments were performed on conscious rabbits that were instrumented with intraabdominal arterial and venous catheters, and diaphragmatic and abdominal electromyographic electrodes. Colorectal distension was achieved by inflation of an acutely placed colorectal balloon catheter until mean arterial pressure increased 10-15 mmHg. Buprenorphine (0.06 mg) or saline was administered intravenously prior to, or during colorectal distension. Arterial blood pressure, heart rate, respiratory rate, abdominal electromyographic activity, and intra-balloon pressure were monitored. In the absence of colorectal distension, buprenorphine increased arterial blood pressure and decreased respiratory rate but did not change heart rate. Colorectal distension increased arterial blood pressure and heart rate, and decreased respiratory rate. The increase in arterial blood pressure associated with colorectal distension was attenuated following preemptive buprenorphine, but was not changed by buprenorphine administered during distension. If cardiovascular changes reflect the intensity of noxious stimulation, then these results support the preemptive administration of buprenorphine for visceral analgesia.

  6. Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy greyhound dogs.

    Science.gov (United States)

    KuKanich, B; Allen, P

    2014-12-01

    The purpose of this study was to compare the pharmacokinetics of two highly protein-bound, lipophilic opioid drugs. Fentanyl (10 μg/kg) and buprenorphine (20 μg/kg) were administered intravenously (IV) to six healthy greyhound dogs (three males and three females). The doses were based on clinically administered doses for dogs. Plasma drug concentrations were determined using liquid chromatography with mass spectrometry, and noncompartmental pharmacokinetics were estimated with computer software. The volume of distribution (area) was larger for fentanyl (7.42 L/kg) compared to buprenorphine (3.54 L/kg). The plasma clearance of fentanyl (38.6 mL·min/kg) was faster than buprenorphine (10.3 mL·min/kg). The terminal half-life of fentanyl (2.22 h) was shorter than buprenorphine (3.96 h). Despite similar physicochemical properties including octanol-water partition coefficient and pKa, the pharmacokinetics of fentanyl and buprenorphine were not similar. Both fentanyl (84%) and buprenorphine (95-98%) are considered highly protein bound, but the differences in protein binding may contribute to the lack of similarity of pharmacokinetics in healthy dogs. © 2014 John Wiley & Sons Ltd.

  7. Pharmacokinetics of oral transmucosal and intramuscular dexmedetomidine combined with buprenorphine in cats.

    Science.gov (United States)

    Porters, N; de Rooster, H; Bosmans, T; Baert, K; Cherlet, M; Croubels, S; De Backer, P; Polis, I

    2015-04-01

    Plasma concentrations and pharmacokinetics of dexmedetomidine and buprenorphine after oral transmucosal (OTM) and intramuscular (i.m.) administration of their combination in healthy adult cats were compared. According to a crossover protocol (1-month washout), a combination of dexmedetomidine (40 μg/kg) and buprenorphine (20 μg/kg) was given OTM (buccal cavity) or i.m. (quadriceps muscle) in six female neutered cats. Plasma samples were collected through a jugular catheter during a 24-h period. Plasma dexmedetomidine and buprenorphine concentrations were determined by liquid chromatography-tandem mass spectrometry. Plasma concentration-time data were fitted to compartmental models. For dexmedetomidine and buprenorphine, the area under the plasma concentration-time curve (AUC) and the maximum plasma concentrations (Cmax ) were significantly lower following OTM than following i.m. administration. For buprenorphine, time to reach Cmax was also significantly longer after OTM administration than after i.m. injection. Data suggested that dexmedetomidine (40 μg/kg) combined with buprenorphine (20 μg/kg) is not as well absorbed from the buccal mucosa site as from the intramuscular injection site. © 2014 John Wiley & Sons Ltd.

  8. A randomized controlled trial of prison-initiated buprenorphine: prison outcomes and community treatment entry.

    Science.gov (United States)

    Gordon, Michael S; Kinlock, Timothy W; Schwartz, Robert P; Fitzgerald, Terrence T; O'Grady, Kevin E; Vocci, Frank J

    2014-09-01

    Buprenorphine is a promising treatment for heroin addiction. However, little is known regarding its provision to pre-release prisoners with heroin dependence histories who were not opioid-tolerant, the relative effectiveness of the post-release setting in which it is provided, and gender differences in treatment outcome in this population. This is the first randomized clinical trial of prison-initiated buprenorphine provided to male and female inmates in the US who were previously heroin-dependent prior to incarceration. A total of 211 participants with 3-9 months remaining in prison were randomized to one of four conditions formed by crossing In-Prison Treatment Condition (received buprenorphine vs. counseling only) and Post-release Service Setting (at an opioid treatment center vs. a community health center). Outcome measures were: entered prison treatment; completed prison treatment; and entered community treatment 10 days post-release. There was a significant main effect (p=.006) for entering prison treatment favoring the In-Prison buprenorphine Treatment Condition (99.0% vs. 80.4%). Regarding completing prison treatment, the only significant effect was Gender, with women significantly (pPrison buprenorphine Treatment Condition (47.5% vs. 33.7%). Buprenorphine appears feasible and acceptable to prisoners who were not opioid-tolerant and can facilitate community treatment entry. However, concerns remain with in-prison treatment termination due to attempted diversion of medication. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Retention in buprenorphine treatment is associated with improved HCV care outcomes.

    Science.gov (United States)

    Norton, B L; Beitin, A; Glenn, M; DeLuca, J; Litwin, A H; Cunningham, C O

    2017-04-01

    Persons who inject drugs, most of whom are opioid dependent, comprise the majority of the HCV infected in the United States. As the national opioid epidemic unfolds, increasing numbers of people are entering the medical system to access treatment for opioid use disorder, specifically with buprenorphine. Yet little is known about HCV care in patients accessing buprenorphine-based opioid treatment. We sought to determine the HCV prevalence, cascade of care, and the association between patient characteristics and completion of HCV cascade of care milestones for patients initiating buprenorphine treatment. We reviewed electronic health records of all patients who initiated buprenorphine treatment at a primary-care clinic in the Bronx, NY between January 2009 and January 2014. Of the 390 patients who initiated buprenorphine treatment, 123 were confirmed to have chronic HCV infection. The only patient characteristic associated with achieving HCV care milestones was retention in opioid treatment. Patients retained (vs. not retained) in buprenorphine treatment were more likely to be referred for HCV specialty care (63.1% vs. 34.0%, pbuprenorphine treatment, there is an unprecedented opportunity to access and treat persons with HCV, reducing HCV transmission, morbidity and mortality. Retention in opioid treatment may improve linkage and retention in HCV care; innovative models of care that integrate opioid drug treatment with HCV treatment are essential. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Use of Buprenorphine in treatment of refractory depression-A review of current literature.

    Science.gov (United States)

    Stanciu, Cornel N; Glass, Oliver M; Penders, Thomas M

    2017-04-01

    Current treatment strategies for depressive disorders have limited efficacy, leaving many patients unimproved or with significant residual symptoms. The development of additional treatments represent a significant unmet need for providers. Several lines of evidence suggest that the opioid system may be involved in regulation of mood and incentives salience. Intervention based on modifying central opioid receptors may represent a novel approach to treatment of depressive disorders among those unresponsive to accepted treatments. We searched the English language literature using keywords: Buprenorphine AND Major Depression; Buprenorphine AND Bipolar Depression; Buprenorphine AND Affective Disorders. Use of low dose buprenorphine as augmentation of pharmacotherapy for depression has shown promise in several reported studies. Effect size of available randomized controlled studies is comparable if not greater than most accepted augmentation strategies. Review of available literature on the use of buprenorphine in individuals with treatment resistant depression demonstrated efficacy in the treatment of depressive disorders. Further prospective randomized controlled trials should be undertaken to evaluate the efficacy of buprenorphine as an adjunct for depression refractory to current pharmacotherapies. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Development of a radioimmunoassay for the determination of buprenorphine in biological samples

    Energy Technology Data Exchange (ETDEWEB)

    Debrabandere, L.; Boven, M. Van; Daenens, P. (Louvain Univ. (Belgium))

    1993-02-01

    The development of a specific and sensitive radioimmunoassay for the detection of buprenorphine in urine samples is described. With minor adjustments, the assay was also applied to the analysis for buprenorphine in plasma samples. The 2-diazobenzoic acid derivative of buprenorphine has been prepared as a hapten. The immunization of rabbits with the hapten-bovine serum albumin conjugate resulted in the production of antibodies, which cross-reacted with N-dealkylbuprenophine up to about the 90% level. The antibodies showed very low cross-reactivities with the 3-O-glucuronides and with the structural analogue etorphine. The assay was mainly used to prescreen for buprenorphine in urine samples of persons suspected of Temgesic misuse and to determine buprenorphine in plasma samples. A linear calibration graph for buprenorphine was obtained after logit-log regression. The spiking recovery study showed a linear regression. Intra-and inter-assay relative standard deviations were < 4.35 and < 6.36%, respectively. A comparison study of the high-performance liquid chromatographic determination (X) to the radioimmunoassay (Y) resulted in the following regression equation for the urine samples: Y = 1.44 + 1.64 X (n = 32; r 0.910) and Y = 0.007 + 1.58 X (n = 10; r = 0.930) for plasma specimens. The minimum detectable dose of the immunoassay was calculated to be 10 pg ml[sup -1] (Student's t-distribution, p 0.01, degrees of freedom = 8). (Author).

  12. Buprenorphine-related complications in elderly hospitalised patients: a case series.

    Science.gov (United States)

    Richards, S; Torre, L; Lawther, B

    2017-03-01

    We report a case series of buprenorphine-related respiratory and neurological depression in opioid-naïve elderly hospitalised patients who received buprenorphine for acute pain management at our institution over a 24-month period. All six patients had risk factors for respiratory depression such as advanced age, concurrent comorbidities, or the ingestion of other potential central nervous system depressants. All patients required escalation of management with additional monitoring, with some transferred to a high dependency or intensive care unit. Five patients had attempted naloxone reversal with varying results. Our cases highlight the fact that while buprenorphine has been demonstrated to have a ceiling effect in relation to respiratory depression in healthy volunteers, it remains an important side-effect and may result in significant respiratory depression in patients with reduced respiratory or neurological reserve. Difficulties with buprenorphine's reversal using naloxone are described. We recommend additional caution when considering buprenorphine for acute pain management in elderly opioid-naïve patients, especially if they have comorbidities or are taking other central nervous system depressants. When buprenorphine is used in patients with risk factors, we recommend additional monitoring and education about potential adverse respiratory effects and their management.

  13. A Retrospective Evaluation of Inpatient Transfer from High-Dose Methadone to Buprenorphine Substitution Therapy.

    Science.gov (United States)

    Oretti, Rossana

    2015-10-01

    The product license of buprenorphine/naloxone for opioid substitution therapy indicates reducing methadone concentrations to 30 mg or less per day for a minimum of 1 week before transferring patients to buprenorphine and no sooner than 24 hours after the last methadone dose, because of the risk of precipitated withdrawal and a corresponding high risk of relapse to opioid use. There are few studies describing high-dose methadone transfers. This retrospective case review assessed the feasibility of transferring patients on methadone doses above 30 mg/day to buprenorphine or buprenorphine/naloxone in the inpatient setting. Six of seven patients on 60-120 mg/day of methadone successfully completed the transfer, and four cases tested negative for opiates at long-term follow-up (6-15 months). This suggests that methadone transfer to buprenorphine can be performed rapidly without the need to taper methadone doses in patients indicated for a therapeutic switch. This small study is hypothesis-generating; larger, well-designed trials are needed to define a protocol that can be used routinely to improve and widen transfers to buprenorphine when indicated. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Combined administration of buprenorphine and naltrexone produces antidepressant-like effects in mice

    Science.gov (United States)

    Almatroudi, Abdulrahman; Husbands, Stephen M.; Bailey, Christopher P.; Bailey, Sarah J.

    2016-01-01

    Opiates have been used historically for the treatment of depression. Renewed interest in the use of opiates as antidepressants has focussed on the development of kappa opioid receptor (κ-receptor) antagonists. Buprenorphine acts as a partial μ-opioid receptor agonist and a κ-receptor antagonist. By combining buprenorphine with the opioid antagonist naltrexone, the activation of μ-opioid receptors would be reduced and the κ-antagonist properties enhanced. We have established that a combination dose of buprenorphine (1mg/kg) with naltrexone (1mg/kg) functions as a short-acting κ-antagonist in the mouse tail withdrawal test. Furthermore, this dose combination is neither rewarding nor aversive in the conditioned place preference paradigm and is without significant locomotor effects. We have shown for the first time that systemic co-administration of buprenorphine (1mg/kg) with naltrexone (1mg/kg) in CD-1 mice produced significant antidepressant-like responses in behaviours in both the forced swim test and novelty induced hypophagia task. Behaviours in the elevated plus maze and light dark box were not significantly altered by treatment with buprenorphine alone, or in combination with naltrexone. We propose that the combination of buprenorphine with naltrexone represents a novel, and potentially a readily translatable approach, to the treatment of depression. PMID:26045511

  15. Revised Dose Schema of Sublingual Buprenorphine in the Treatment of the Neonatal Opioid Abstinence Syndrome

    Science.gov (United States)

    Kraft, Walter K.; Dysart, Kevin; Greenspan, Jay S.; Gibson, Eric; Kaltenbach, Karol; Ehrlich, Michelle E.

    2010-01-01

    AIMS Over half of infants exposed to opioids in utero develop neonatal abstinence syndrome (NAS) of severity to require pharmacologic therapy. Current treatments are associated with prolonged hospitalization. We sought to optimize the dose of sublingual buprenorphine in the treatment of NAS. DESIGN Randomized, phase 1, open-label, active-control clinical trial comparing sublingual buprenorphine to oral morphine. SETTING Large, urban, tertiary care hospital. PARTICIPANTS Twenty-four term infants requiring pharmacological treatment for NAS. MEASUREMENTS Outcomes were neonatal safety, length of treatment, and length of hospitalization. FINDINGS Sublingual buprenorphine was safe and effective. Infants treated with buprenorphine had a 23-day length of treatment compared to 38 days for those treated with morphine (p=0.01), representing a 40% reduction. Length of hospital stay in the buprenorphine group was reduced 24%, from 42 to 32 days (p=0.05). CONCLUSIONS Sublingual buprenorphine was safe in NAS, with a substantial efficacy advantage over standard of care therapy with oral morphine. PMID:20925688

  16. Intraoperative end-tidal concentration of isoflurane in cats undergoing ovariectomy that received tramadol, buprenorphine or a combination of both.

    Science.gov (United States)

    Bellini, Luca; Mollo, Antonio; Contiero, Barbara; Busetto, Roberto

    2017-02-01

    Objectives The aim of the study was to evaluate the end-tidal concentration of isoflurane required to maintain heart and respiratory rate within ± 20% of basal measurement in cats undergoing ovariectomy that received buprenorphine, tramadol or a combination of both. Methods Thirty cats, divided into three groups, were enrolled in a simple operator-blinded, randomised study. Cats received acepromazine (0.03 mg/kg) and one of the following treatments: buprenorphine (0.02 mg/kg), tramadol (2 mg/kg) or a combination of both. Anaesthesia was induced with propofol and maintained with isoflurane titrated in order to maintain heart and respiratory rate within the target values recorded before premedication. Results Groups were similar for age, weight, dose of propofol administered, sedation and recovery scores. Cats receiving tramadol with buprenorphine were extubated earlier after isoflurane discontinuation. No statistical differences were detected in end-tidal fraction of isoflurane between buprenorphine alone or with tramadol. In cats that received tramadol or buprenorphine alone, ovarian pedicle traction caused a statistical increase in end-tidal isoflurane concentration compared with that measured during incision and suture of the skin. In cats that received the combination of tramadol plus buprenorphine no differences among surgical time points were observed. Conclusions and relevance Tramadol added to buprenorphine did not provide any advantage in decreasing the end-tidal fraction of isoflurane compared with buprenorphine alone, although it is speculated there may be an infra-additive interaction between tramadol and buprenorphine in cats.

  17. Effects of buprenorphine and meloxicam analgesia on induced cerebral ischemia in C57BL/6 male mice

    DEFF Research Database (Denmark)

    Jacobsen, Kirsten R; Fauerby, Natasha; Raida, Zindy

    2013-01-01

    investigated whether buprenorphine and meloxicam, at clinically relevant doses provided pain relief without altering infarct volume in male C57BL/6 mice. Common known side-effects of buprenorphine, including decreased food consumption, were noted after surgery in buprenorphine-treated mice, but these effects...... were brief and seen only during the treatment period. Fecal corticosterone metabolites did not differ significantly between the groups. In the present study, buprenorphine treatment did not alter infarction volume when compared with that of mice that did not receive analgesia. In contrast, meloxicam...

  18. Non-Prescribed Buprenorphine in New York City: Motivations for Use, Practices of Diversion, and Experiences of Stigma.

    Science.gov (United States)

    Allen, Bennett; Harocopos, Alex

    2016-11-01

    Non-medical use of opioid analgesics (OAs) has increased in the United States over the past decade. Concurrently, access to opioid agonist therapies (OATs) such as buprenorphine has expanded. However, there has been little in-depth qualitative exploration into circumstances surrounding buprenorphine diversion and non-prescribed use. This study reports on qualitative data from in-depth interviews conducted with persons in New York City reporting non-medical OA use in the past 12 months. Participants (n=42) were aged between 18 and 49 years. The majority were male (n=29) and non-Hispanic White (n=35). All participants self-reported physical opioid dependence. Motivations for non-prescribed buprenorphine use included the abatement of withdrawal symptoms or a self-initiated detoxification or treatment plan. Few participants reported buprenorphine use for euphoric effect, and no participants reported using buprenorphine as a primary drug. Buprenorphine diversion primarily occurred as a means of supporting ongoing illicit drug use, and no participants reported selling buprenorphine as a primary source of income. Participants reported misinformation around some key areas of buprenorphine induction and use, as well as stigma within peer networks and from drug treatment providers. As access to buprenorphine treatment continues to expand in the United States, enhancing patient education is a critical step toward minimizing diversion and incidental harms from non-prescribed use. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. [The peculiarities of the comprehensive study of buprenorphine].

    Science.gov (United States)

    Lobacheva, G K; Simonov, E A; Kuzovlev, V Yu; Kairgaliev, D V; Gavrilin, Yu V; Atroshchenko, Yu M

    The authors describe the methods of pharmaceutical and criminalistics analysis that are finding the increasingly wider application for the drug expertise (identification) and elucidation of the circumstances conducive to the commission of an offence. The special emphasis is laid on the buprenorphine studies with the use of the colour chemical reactions, thin-layer chromatography, gas chromatographic analysis, high-performance liquid chromatography, IR spectrometry, and other modern techniques. The methods based on the recent achievements in pharmaceutical and criminalistics sciences can be employed in the activities intended to control the illegal drug circulation. Moreover, they may be of importance for obtaining valuable information about the actions of the persons involved in the trafficking or synthesis (production) of the prohibited substances after they are brought to criminal responsibility and/or appear before the court.

  20. Evaluation of the Pharmacokinetics of Single- and Multiple-dose Buprenorphine Buccal Film in Healthy Volunteers.

    Science.gov (United States)

    Bai, Stephen A; Xiang, Qinfang; Finn, Andrew

    2016-02-01

    Buprenorphine, a partial μ-receptor agonist, is approved for the management of moderate to severe pain, but it has low oral bioavailability. Two open-label studies were performed to determine the pharmacokinetic profile of buprenorphine from buccal film formulations of buprenorphine. Both studies enrolled healthy volunteers, aged 18 to 55 years, who received concurrent oral naltrexone to reduce adverse events (AEs); subjects with a history or evidence of substance abuse or current use of any product affecting cytochrome P450 3A4 activity were excluded. The first study (n = 25) was a 5-period crossover trial with 4 single doses (75 and 300 and 300 and 1200 μg) of 2 formulations (F14 and F24) of buccal buprenorphine (BBUP) and a 300-μg intravenous dose of buprenorphine with a 7-day washout between periods. In the second study, each subject (n = 10) received 6 doses of 4 BBUP strengths (60, 120, 180, and 240 μg BID) in a dose-escalation design. Plasma concentrations of buprenorphine and norbuprenorphine were assayed, and pharmacokinetics were summarized with descriptive statistics and analyzed by using a linear mixed effects model (single-dose study). AEs were recorded. In the single-dose study, the 2 formulations exhibited comparable bioavailability of 46% to 51% that was independent of dose, with a single buprenorphine peak concentration from each BBUP dose occurring at 2.5 to 3 hours. The mean buprenorphine Cmax across the doses ranged from 0.17 ng/mL for the 75-µg dose to 1.43 ng/mL for the 1200-µg dose. AUC0-∞, AUC0-last, and Cmax were proportional to the dose of BBUP administered. Cmax of norbuprenorphine after BBUP administration was approximately one tenth that of buprenorphine Cmax. In the multiple-dose study, steady state was reached within 3 days of BID dosing. There was a linear increase in exposure across the dose range from 60 to 240 μg BID. Treatment-emergent AEs in both studies were consistent with those reported with opiate administration to

  1. Cocaine Use Reduction with Buprenorphine (CURB): Rationale, design, and methodology☆

    Science.gov (United States)

    Mooney, Larissa J.; Nielsen, Suzanne; Saxon, Andrew; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Stablein, Don; McCormack, Jennifer; Lindblad, Robert; Ling, Walter

    2013-01-01

    Background Effective medications to treat cocaine dependence have not been identified. Recent pharmacotherapy trials demonstrate the potential efficacy of buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The National Institute on Drug Abuse Clinical Trials Network (CTN) launched the Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the safety and efficacy of sublingual BUP (as Suboxone®) in the presence of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) for the treatment of cocaine dependence. This paper describes the design and rationale for this study. Methods This multi-site, double-blind, placebo-controlled study will randomize 300 participants across 11 sites. Participants must meet the DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Participants are inducted onto XR-NTX after self-reporting at least 7 days of abstinence from opioids and tolerating a naloxone challenge followed by oral naltrexone and are then randomly assigned to one of three medication conditions (4 mg BUP, 16 mg BUP, or placebo) for 8 weeks. Participants receive a second injection of XR-NTX 4 weeks after the initial injection, and follow-up visits are scheduled at 1 and 3 months post-treatment. Participants receive weekly cognitive behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment, active medication, and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates. Conclusions This research using 2 medications will demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine use in adults with cocaine dependence and opioid use disorders and will demonstrate if XR-NTX prevents development of physiologic dependence on BUP. PMID:23159524

  2. Cocaine use reduction with buprenorphine (CURB): rationale, design, and methodology.

    Science.gov (United States)

    Mooney, Larissa J; Nielsen, Suzanne; Saxon, Andrew; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Stablein, Don; McCormack, Jennifer; Lindblad, Robert; Ling, Walter

    2013-03-01

    Effective medications to treat cocaine dependence have not been identified. Recent pharmacotherapy trials demonstrate the potential efficacy of buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The National Institute on Drug Abuse Clinical Trials Network (CTN) launched the Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the safety and efficacy of sublingual BUP (as Suboxone®) in the presence of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) for the treatment of cocaine dependence. This paper describes the design and rationale for this study. This multi-site, double-blind, placebo-controlled study will randomize 300 participants across 11 sites. Participants must meet the DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Participants are inducted onto XR-NTX after self-reporting at least 7 days of abstinence from opioids and tolerating a naloxone challenge followed by oral naltrexone and are then randomly assigned to one of three medication conditions (4 mg BUP, 16 mg BUP, or placebo) for 8 weeks. Participants receive a second injection of XR-NTX 4 weeks after the initial injection, and follow-up visits are scheduled at 1 and 3 months post-treatment. Participants receive weekly cognitive behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment, active medication, and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates. This research using 2 medications will demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine use in adults with cocaine dependence and opioid use disorders and will demonstrate if XR-NTX prevents development of physiologic dependence on BUP. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Clinical efficacy of buprenorphine to minimize distress in MRL/lpr mice

    Science.gov (United States)

    Swenson, Julie; Olgun, Selen; Radjavi, Ali; Kaur, Taranjit; Reilly, Christopher M.

    2007-01-01

    MRL/MpJ-Faslpr (MRL/lpr) mice are an accepted animal model to study human systemic lupus erythematosus. We tested if a commonly used analgesic (buprenorphine hydrochloride) would reduce pain and distress in these mice without impacting the progression of autoimmune disease. Female MRL/lpr mice were randomly separated into four groups. Experimental groups received cyclophosphamide (25 mg/kg i.p. weekly), buprenorphine (0.09 mg/kg/mouse/day via drinking water), or cyclophosphamide + buprenorphine from 11 - 21 weeks of age. Controls received no treatments. Mice were monitored daily by a licensed veterinarian (blinded observer) and assigned a score weekly on parameters associated with pain and distress as well as progression of disease. Proteinuria was measured weekly, and serum anti-dsDNA antibody levels were determined at 11, 15, and 18 weeks of age. At 21 weeks of age, the animals were euthanized and the kidneys and spleens were removed for evaluation. Regardless of the parameter observed, buprenorphine did not significantly decrease distress when compared to the controls. Buprenorphine did not alter the progression of autoimmune disease, based on characteristics of splenic architecture and splenocyte cell profiles, development of lymphadenopathy, or kidney histology as compared to controls. This study indicates that buprenorphine at this dose and route of administration was ineffective in reducing distress associated with disease progression in the MRL/lpr strain. More studies are needed to determine if, at a different dose or route, buprenorphine would be useful as adjunctive therapy in reducing distress in MRL/lpr mice. PMID:17490635

  4. Anaesthesia with a combination of ketamine and medetomidine in the rabbit: effect of premedication with buprenorphine.

    Science.gov (United States)

    Murphy, Kathy L; Roughan, Johnny V; Baxter, Mark G; Flecknell, Paul A

    2010-05-01

    To assess the effects of premedication with buprenorphine on the characteristics of anaesthesia induced with ketamine/medetomidine. Prospective crossover laboratory study. Six female New Zealand White rabbits. Rabbits received, on occasions separated by 7 days, either buprenorphine (0.03 mg kg(-1)) or saline subcutaneously (SC) as premedication, followed 1 hour later by SC ketamine (15 mg kg(-1)) and medetomidine (0.25 mg kg(-1)) (K/M). At pre-determined time points reflex responses and cardiopulmonary parameters were recorded and arterial blood samples taken for analysis. Total sleep time was the duration of loss of the righting reflex. Duration of surgical anaesthesia was the time of suppression of the ear pinch and pedal withdrawal reflexes. Wilcoxon signed-ranks tests were used to compare data before (T(0)) and 10 minutes after (T(10)) injection with K/M. All animals lost all three reflex responses within 10 minutes of injection of K/M. The duration of loss of these reflexes significantly increased in animals that received buprenorphine. At induction, animals that had received buprenorphine tended to have a lower respiration rate but there were no significant differences in arterial PCO(2), PO(2) or pH between treatments. Hypoxaemia [median PaO(2) buprenorphine. Premedication with buprenorphine significantly increased the duration of anaesthesia induced by K/M, with no significant depression of respiration further to the control treatment within the first 10 minutes of anaesthesia. The MAP decreased but this was not reflected in a difference in other physiological parameters. These data show that premedication with buprenorphine, before K/M anaesthesia in the rabbit, has few negative effects and may provide beneficial analgesia.

  5. Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site.

    Science.gov (United States)

    Messenger, Kristen M; Davis, Jennifer L; LaFevers, Douglas H; Barlow, Beth M; Posner, Lysa P

    2011-07-01

    To describe the pharmacokinetics and adverse effects of intravenous (IV) and sublingual (SL) buprenorphine in horses, and to determine the effect of sampling site on plasma concentrations after SL administration. Randomized crossover experiment; prospective study. Eleven healthy adult horses between 6 and 20 years of age and weighing 487-592 kg. In the first phase; buprenorphine was administered as a single IV or SL dose (0.006 mg kg(-1)) and pharmacokinetic parameters were determined for each route of administration using a noncompartmental model. In the second phase; the jugular and lateral thoracic veins were catheterized for simultaneous venous blood sampling, following a dose of 0.006 mg kg(-1) SL buprenorphine. For both phases, plasma buprenorphine concentrations were measured using ultra-performance liquid chromatography with mass spectrometry. At each sampling period, horses were assessed for behavioral excitement and gastrointestinal motility. Following IV administration, buprenorphine mean ± SD half-life was 5.79 ± 1.09 hours. Systemic clearance (Cl) following IV administration was 6.13 ± 0.86 mL kg(-1) minute(-1) and volume of distribution at steady-state was 3.16 ± 0.65 L kg(-1). Following IV administration, horses showed signs of excitement. Gastrointestinal sounds were decreased following both routes of administration; however, none of the horses exhibited signs of colic. There was a significant discrepancy between plasma buprenorphine concentrations measured in the jugular vein versus the lateral thoracic vein following phase 2, thus pharmacokinetic parameters following SL buprenorphine are not reported. Buprenorphine has a long plasma half-life and results in plasma concentrations that are consistent with analgesia in other species for up to 4 hours following IV administration of this dose in horses. While buprenorphine is absorbed into the circulation following SL administration, jugular venous sampling gave a false measurement of the quantity

  6. Benzodiazepine use during buprenorphine treatment for opioid dependence: clinical and safety outcomes.

    Science.gov (United States)

    Schuman-Olivier, Zev; Hoeppner, Bettina B; Weiss, Roger D; Borodovsky, Jacob; Shaffer, Howard J; Albanese, Mark J

    2013-10-01

    Prescribing benzodiazepines during buprenorphine treatment is a topic of active discussion. Clinical benefit is unclear. Overdose, accidental injury, and benzodiazepine misuse remain concerns. We examine the relationship between benzodiazepine misuse history, benzodiazepine prescription, and both clinical and safety outcomes during buprenorphine treatment. We retrospectively examined outpatient buprenorphine treatment records, classifying patients by past-year benzodiazepine misuse history and approved benzodiazepine prescription at intake. Primary clinical outcomes included 12-month treatment retention and urine toxicology for illicit opioids. Primary safety outcomes included total emergency department (ED) visits and odds of an ED visit related to overdose or accidental injury during treatment. The 12-month treatment retention rate for the sample (N=328) was 40%. Neither benzodiazepine misuse history nor benzodiazepine prescription was associated with treatment retention or illicit opioid use. Poisson regressions of ED visits during buprenorphine treatment revealed more ED visits among those with a benzodiazepine prescription versus those without (pbenzodiazepine misuse history had no effect. The odds of an accidental injury-related ED visit during treatment were greater among those with a benzodiazepine prescription (OR: 3.7, pbenzodiazepine misuse history or prescription. We found no effect of benzodiazepine prescriptions on opioid treatment outcomes; however, benzodiazepine prescription was associated with more frequent ED visits and accidental injuries, especially among females. When prescribing benzodiazepines during buprenorphine treatment, patients need more education about accidental injury risk. Alternative treatments for anxiety should be considered when possible, especially among females. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Anxiety Treatment of Opioid Dependent Patients with Buprenorphine: A Randomized, Double-blind, Clinical Trial.

    Science.gov (United States)

    Ahmadi, Jamshid; Jahromi, Mina Sefidfard

    2017-01-01

    The objective of this study is to examine the impact of vary doses of buprenorphine on anxiety symptoms in opioid-dependent inpatients over a 7 days period, using a randomized controlled trial design. Patients were randomized to three groups. Fourteen men who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for both opioid use disorder and generalized anxiety disorder and were seeking for treatment. Patients obtain dosages of 32 mg or 64 mg or 96 mg of buprenorphine as a single dose only and were treated in a psychiatric inpatient unit. Of 14 subjects; 5 (35.7%) obtained 32 mg, 4 (28.6%) obtained 64 mg, and 5 (35.7%) obtained 96 mg of buprenorphine. Administering daily Hamilton Anxiety Rating Scale and interview. All the patients ended the 7-day treatment time. The results showed a significant reduction in anxiety symptoms within each of the three groups (P = 0.00), but no difference in outcome between the groups (P = 0.605). The outcome suggests a single high dose of buprenorphine can supply a speedy, safe, simple, and suitable means of anxiety treatment. The single high dose of buprenorphine could be a novel mechanism medication that provides a rapid and sustained improvement for generalized anxiety disorder in opioid dependent patients. Placebo-controlled trials of longer duration are needed to evaluate ability, safety, and psychological and physiological influence of extended exposure to this medication.

  8. Validated Spectrophtometric Method for Simultaneous Determination of Buprenorphine and Naloxone in Pharmaceutical Dosage Forms

    Science.gov (United States)

    Souri, Effat; Ahmadi, Farzaneh Sadat; Barazandeh Tehrani, Maliheh; Hosseini, Majid Mohammad; Fadaye Vatan, Sedigheh

    2017-01-01

    Buprenorphine is a partial mu agonist and kappa antagonist which is used for the treatment of pain and opioid addiction. A mixture of buprenorphine hydrochloride and naloxone hydrochloride has been approved for the treatment of opioid dependence. In this study a third order derivative spectrophotometric method based on zero-crossing technique has been used for the simultaneous determination of buprenorphine hydrochloride and naloxone hydrochloride in tablets. The measurements were carried out at wavelengths of 257.8 (zero-crossing point of naloxone hydrochloride) and 252.2 nm (zero-crossing point of buprenorphice hydrochloride) for buprenorphine hydrochloride and naloxone hydrochloride, respectively in the third order derivative spectra obtained in methanol and 0.1 M NaOH (50:50) as solvent. The method was found to be linear in the range of 20-80 µg/mL for buprenorphine hydrochloride and 5-20 µg/mL for naloxone hydrochloride. The within-day and between-day coefficient of variation and error values were less than 2.5% and 1.8%, respectively. The proposed method was successfully used for simultaneous determination of these drugs in pharmaceutical dosage form without any interference from excipients or need to prior separation before analysis. PMID:28496466

  9. Transfer of buprenorphine into breast milk and calculation of infant drug dose.

    Science.gov (United States)

    Lindemalm, Synnove; Nydert, Per; Svensson, Jan-Olov; Stahle, Lars; Sarman, Ihsan

    2009-05-01

    Little is known about the safety of buprenorphine (BUP) in breastfeeding. The aim of this work was to investigate the transfer of buprenorphine and its main active metabolite, norbuprenorphine (n-BUP), into human milk and to determine the drug dose and effects in exposed infants. Seven lactating women, who were maintained on BUP treatment because of previous opiate addiction, were studied in an open observational study. All mothers had a strong wish to breastfeed their newborn infants. Buprenorphine samples for analysis were collected from the urine of 6 infants together with breast milk, blood, and urine from their mothers during a 24-hour period in the week after birth. One mother-infant pair was studied at 9 months of age. Buprenorphine and n-BUP were analyzed by a liquid chromatography/mass spectrometry method suitable for handling different matrices. Buprenorphine and n-BUP were found in low levels in the infants' urine. Breastfed infants were exposed to a calculated BUP dose per kg bodyweight less than 1%, with an average milk/plasma area under the curve of 1.7 (range, 1.1-2.8) for BUP and 0.7 (range, 0.4-1.2) for n-BUP. These data support the use of BUP during breastfeeding. However, the authors recommend that infants be monitored closely.

  10. Treatment of Opioid Dependence With Buprenorphine/Naloxone After Liver Transplantation: Report of Two Cases.

    Science.gov (United States)

    Aldemir, E; Coskunol, H; Kilic, M; Sert, I

    2016-10-01

    Opioid dependence is an increasing public health problem. One of the complications of intravenous opioid use is hepatitis C virus infection, which, in turn, is one of the most common indications for liver transplantations throughout the world. Therefore, the treatment of opioid dependence in a liver transplant recipient requires special attention in terms of graft function, drug interactions, and patient compliance. Buprenorphine is a semi-synthetic opioid-derived agent with analgesic effects. To prevent buprenorphine abuse, it is combined with the opioid antagonist naloxone. This buprenorphine/naloxone combination is the only drug approved for the treatment of opioid dependence in Turkey. Although the literature includes data about the safe usage of buprenorphine in liver transplantation in animals, there is no such evidence in either case reports or clinical trials for the same in humans. In this article, we present a report of our treatment of 2 opioid-dependent patients with buprenorphine/naloxone after liver transplantation due to hepatitis C virus-induced liver cirrhosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Evaluation of sedation for standing clinical procedures in horses using detomidine combined with buprenorphine.

    Science.gov (United States)

    Taylor, Polly; Coumbe, Karen; Henson, Frances; Scott, David; Taylor, Alan

    2014-01-01

    To examine the effect of including buprenorphine with detomidine for sedation of horses undergoing clinical procedures. Partially blinded, randomised, prospective clinical field trial. Eighty four client-owned horses scheduled for minor surgery or diagnostic investigation under standing sedation. The effects of buprenorphine (5 μg kg(-1) ) (Group B, n = 46) or placebo (5% glucose solution) (Group C, n = 38) in combination with detomidine (10 μg kg(-1) ) were compared in standing horses undergoing minor clinical procedures. The primary outcome measure was successful completion of the procedure. The degree of sedation and ataxia were scored using simple descriptive scales. Heart and respiratory rates were recorded at 15-30 minute intervals. Parametric data from each group were compared using anova or t-test and non parametric data using the Mann-Whitney U test. The procedure was carried out successfully in 91% of Group B and 63% of Group C (p buprenorphine but not glucose administration, was more profound in group B and lasted longer (60 versus 30 minutes) p Buprenorphine 5 and 10 μg kg(-1) enhanced the sedation produced by detomidine 10 and 20 μg kg(-1) with minor side effects similar to other alpha2 agonist/opioid combinations. Detomidine-buprenorphine sedation is suitable for standing procedures in horses. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  12. Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus).

    Science.gov (United States)

    Taylor, Bryan F; Ramirez, Harvey E; Battles, August H; Andrutis, Karl A; Neubert, John K

    2016-01-01

    Effective pain management for rats and mice is crucial due to the continuing increase in the use of these species in biomedical research. Here we used a recently validated operant orofacial pain assay to determine dose-response curves for buprenorphine and tramadol when mixed in nut paste and administered to male and female rats. Statistically significant analgesic doses of tramadol in nut paste included doses of 20, 30, and 40 mg/kg for female rats but only 40 mg/kg for male rats. For male rats receiving buprenorphine mixed in nut paste, a significant analgesic response was observed at 0.5 and 0.6 mg/kg. None of the doses tested produced a significant analgesic response in female rats. Our results indicate that at the doses tested, tramadol and buprenorphine produced an analgesic response in male rats. In female rats, tramadol shows a higher analgesic effect than buprenorphine. The analgesic effects observed 60 min after administration of the statistically significant oral doses of both drugs were similar to the analgesic effects of 0.03 mg/kg subcutaneous buprenorphine 30 min after administration. The method of voluntary ingestion could be effective, is easy to use, and would minimize stress to the rats during the immediate postoperative period.

  13. State policy influence on the early diffusion of buprenorphine in community treatment programs

    Directory of Open Access Journals (Sweden)

    Abraham Amanda J

    2008-06-01

    Full Text Available Abstract Background Buprenorphine was approved for use in the treatment of opioid dependence in 2002, but its diffusion into everyday clinical practice in community-based treatment programs has been slow. This study examines the net impact of efforts by state agencies, including provision of Medicaid coverage, on program-level adoption of buprenorphine as of 2006. Methods Interviews were conducted with key informants in 49 of the 50 state agencies with oversight responsibility for addiction treatment services. Information from these interviews was integrated with organizational data from the 2006 National Survey of Substance Abuse Treatment Services. A multivariate logistic regression model was estimated to identify the effects of state efforts to promote the use of this medication, net of a host of organizational characteristics. Results The availability of Medicaid coverage for buprenorphine was a significant predictor of its adoption by treatment organizations. Conclusion Inclusion of buprenorphine on state Medicaid formularies appears to be a key element in ensuring that patients have access to this state-of-the-art treatment option. Other potential barriers to the diffusion of buprenorphine require identification, and the value of additional state-level policies to promote its use should be evaluated.

  14. Prenatally buprenorphine-exposed children: health to 3 years of age.

    Science.gov (United States)

    Kivistö, Kaisa; Tupola, Sarimari; Kivitie-Kallio, Satu

    2015-11-01

    Our prospective study is among the first attempts to examine the health of prenatally buprenorphine-exposed children after neonatal age and to determine the types of child maltreatment in this patient group. The study population included 102 children (61/41 Caucasian males/females) who had a positive urine screen for buprenorphine as a newborn. In addition to buprenorphine, the children were also prenatally exposed to other substances. The data were collected by pediatricians in follow-up visits until 3 years of age and from medical records. Ten prenatally buprenorphine-exposed children (10 %) had some birth defect. The study children had slightly more major anomalies than newborns on average in Finland (3.4 %). Eye disorders (nystagmus, opticus atrophy, and strabismus) occurred in 11 % of children. One child was diagnosed with hepatitis C transmission. One female died of sudden infant death syndrome (SIDS), and one male died of congenital heart disease. Pediatricians submitted altogether 70 reports to child welfare services of suspected maltreatment. Of these reports, 45 (64 %) involved medical neglect. Physical abuse was suspected in four reports. We suggest that prenatally buprenorphine-exposed children have several types of problems with their health at toddler age and that they are susceptible to child maltreatment, especially to medical neglect.

  15. Post-operative pain relief in children following caudal bupivacaine and buprenorphine--a comparative study.

    Directory of Open Access Journals (Sweden)

    Anilkumar T

    1994-04-01

    Full Text Available Eighty-five paediatric patients (age range: 6 mths-12yrs undergoing lower abdominal surgery were studied for post-operative pain relief following either caudal bupivacaine (GpI: n = 43 or buprenorphine (GpII: n = 42. Bupivacaine was administered as 0.5ml/kg body weight of 0.25% solution and buprenorphine as 4 micrograms/ml and volume of 0.5 ml/Kg body weight in normal saline. Post-operatively pain was graded on a 4-point scale and behaviour on a 5-point scale. Any post-operative complications and need for additional analgesia were also noted. Bupivacaine provided good pain relief in the early post-operative hours but buprenorphine provided pain relief lasting for 24 hrs or more post-operatively. Post-operative behaviour of 10 patients receiving buprenorphine was graded as cheerful as compared to 2 from bupivacaine group. Till the end of observation period (i.e. 8 hr post-operatively, majority of patients receiving buprenorphine remained cheerful.

  16. A Randomized Controlled Trial of Prison-Initiated Buprenorphine: Prison Outcomes and Community Treatment Entry

    Science.gov (United States)

    Gordon, Michael S.; Kinlock, Timothy W.; Schwartz, Robert P.; Fitzgerald, Terrence; O’Grady, Kevin E.; Vocci, Frank J.

    2014-01-01

    Background Buprenorphine is a promising treatment for heroin addiction. However, little is known regarding its provision to pre-release prisoners with heroin dependence histories who were not opioid-tolerant, the relative effectiveness of the post-release setting in which it is provided, and gender differences in treatment outcome in this population. Methods This is the first randomized clinical trial of prison-initiated buprenorphine provided to male and female inmates in the US who were previously heroin-dependent prior to incarceration. A total of 211 participants with 3–9 months remaining in prison were randomized to one of four conditions formed by crossing In-Prison Treatment Condition (received buprenorphine vs. counseling only) and Post-release Service Setting (at an opioid treatment center vs. a community health center). Outcome measures were: entered prison treatment; completed prison treatment; and entered community treatment 10 days post-release. Results There was a significant main effect (p=.006) for entering prison treatment favoring the In-Prison buprenorphine Treatment Condition (99.0% vs. 80.4%). Regarding completing prison treatment, the only significant effect was Gender, with women significantly (pbuprenorphine Treatment Condition (47.5% vs. 33.7%). Conclusions Buprenorphine appears feasible and acceptable to prisoners who were not opioid-tolerant and can facilitate community treatment entry. However, concerns remain with in-prison treatment termination due to attempted diversion of medication. PMID:24962326

  17. The impact of long-term maintenance treatment with buprenorphine on complex psychomotor and cognitive function.

    Science.gov (United States)

    Shmygalev, Sergey; Damm, Martin; Weckbecker, Klaus; Berghaus, Günter; Petzke, Frank; Sabatowski, Rainer

    2011-09-01

    Despite the fact that buprenorphine is effective, well tolerated and due to its pharmacological profile a very safe drug, the impact of long-term buprenorphine substitution therapy on complex psychomotor and cognitive function predicting driving ability is not yet clear. Therefore, a prospective comparison between patients receiving sublingual buprenorphine and a control group of untreated, healthy volunteers was performed. Treated and untreated subjects were matched for age and sex, with three control subjects selected for every buprenorphine patient. Patients using unreported drugs were included in the intention-to-treat (ITT) analysis; the remaining patients were analysed as the per-protocol (PP) group. The test battery comprised the assessment of: performance during stress, visual orientation, concentration, attention, vigilance and reaction time. The primary endpoint was defined as the sum of the relevant scores of the tests after z-transformation of the individual scores. 30 patients with sublingual buprenorphine treatment (7.7±3.9 mg per day) were matched to 90 controls. 19 patients were excluded from the PP-analysis because of additional unreported drug intake. Significant non-inferiority could be demonstrated for the PP-group (pimpact of the drug on driving ability, those patients do not seem to be qualified for getting their driving license. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  18. Clonidine Increases the Likelihood That Abstinence Can Withstand Unstructured Time in Buprenorphine-maintained Outpatients.

    Science.gov (United States)

    Kowalczyk, William J; Bertz, Jeremiah W; Moran, Landhing M; Phillips, Karran A; Ghitza, Udi E; Epstein, David H; Preston, Kenzie L

    In a clinical trial examining daily clonidine as an adjunct to buprenorphine treatment for opioid dependence, we found that clonidine increased opioid abstinence and decoupled stress from craving. From a personalized-medicine perspective, the next step is to identify people for whom clonidine would be beneficial. To that end, using data from the same clinical trial, we examined the associations of daily-life activities with treatment success. Outpatients (N = 118) received clonidine (0.3 mg/d) or placebo during 18 weeks of buprenorphine treatment. Participants carried a smartphone that randomly prompted them 4 times per day to report their moods and activities. Using generalized linear mixed models, we assessed the likelihoods of different types of daily activity as a function of clonidine versus placebo, days of longest continuous opioid abstinence, and their interaction. Participants in the buprenorphine-only (buprenorphine plus placebo) control group who engaged in more responsibilities (work and child/elder care) had longer streaks of abstinence, whereas those who engaged in more unstructured-time activities had shorter streaks of abstinence. Conversely, for participants in the buprenorphine-plus-clonidine group, longer streaks of abstinence were associated with higher frequencies of activities associated with "unstructured" time. The study replicates findings that engaging in responsibilities is related to positive treatment outcomes in standard opioid agonist therapy. The pattern of results also suggests that clonidine helped participants engage in unstructured-time activities with less risk of craving or use than they might otherwise have had.

  19. Evaluation of buprenorphine hydrochloride Pluronic® gel formulation in male C57BL/6NCrl mice

    Science.gov (United States)

    Blankenship-Paris, Terry L.; Dutton, John W.; Goulding, David R.; McGee, Christopher A.; Kissling, Grace E.; Myers, Page H.

    2016-01-01

    Providing adequate analgesia while minimizing handling and stress post-surgery can be challenging. Recently, there have been commercial products made available for providing long acting analgesia in rodents. However, we find there are limitations for use in mice due to the viscosity of the product and the small dosing volumes needed. This project evaluated an in-house compounded formulation of buprenorphine easily made in the laboratory using pharmaceutical grade products. The release of buprenorphine was evaluated when compounded with two types of hydrogels (Pluronic® F-127 and F-68). Mice given buprenorphine in hydrogel (BP) demonstrated higher serum levels of buprenorphine for a longer period of time compared to mice given standard buprenorphine (Bup). However, the rate of decline in serum levels between the groups was similar; thus, it is more likely that the higher buprenorphine concentration seen in the BP group is due to the higher dose of buprenorphine given, rather than a slower release of product. Feed consumption was decreased in both groups one day after dosing; however, there was no difference in body weights. Increased activity in the open field was observed with both buprenorphine formulations, and lipemia was observed in mice given BP which persisted to at least 96 h. Based on our results, we conclude that this formulation did not sustain the release of buprenorphine or eliminate the increased activity commonly seen in mice given buprenorphine. In addition, the lipemia may confound research parameters, especially in cardiac studies and lipid metabolism studies. Therefore, we cannot recommend this formulation for use. PMID:27654688

  20. Evaluation of buprenorphine hydrochloride Pluronic(®) gel formulation in male C57BL/6NCrl mice.

    Science.gov (United States)

    Blankenship-Paris, Terry L; Dutton, John W; Goulding, David R; McGee, Christopher A; Kissling, Grace E; Myers, Page H

    2016-09-21

    Providing adequate analgesia while minimizing handling and stress post-surgery can be challenging. Recently, there have been commercial products made available for providing long acting analgesia in rodents. However, we find there are limitations for use in mice due to the viscosity of the product and the small dosing volumes needed. This project evaluated an in-house compounded formulation of buprenorphine easily made in the laboratory using pharmaceutical grade products. The release of buprenorphine was evaluated when compounded with two types of hydrogels (Pluronic(®) F-127 and F-68). Mice given buprenorphine in hydrogel (BP) demonstrated higher serum levels of buprenorphine for a longer period of time compared to mice given standard buprenorphine (Bup). However, the rate of decline in serum levels between the groups was similar; thus, it is more likely that the higher buprenorphine concentration seen in the BP group is due to the higher dose of buprenorphine given, rather than a slower release of product. Feed consumption was decreased in both groups one day after dosing; however, there was no difference in body weights. Increased activity in the open field was observed with both buprenorphine formulations, and lipemia was observed in mice given BP which persisted to at least 96 h. Based on our results, we conclude that this formulation did not sustain the release of buprenorphine or eliminate the increased activity commonly seen in mice given buprenorphine. In addition, the lipemia may confound research parameters, especially in cardiac studies and lipid metabolism studies. Therefore, we cannot recommend this formulation for use.

  1. Clinical Efficacy of Sustained-Release Buprenorphine with Meloxicam for Postoperative Analgesia in Beagle Dogs Undergoing Ovariohysterectomy

    Science.gov (United States)

    Nunamaker, Elizabeth A; Stolarik, DeAnne F; Ma, Junli; Wilsey, Amanda S; Jenkins, Gary J; Medina, Chris L

    2014-01-01

    The goal of the current study was to compare the efficacy, adverse effects, and plasma buprenorphine concentrations of sustained-release buprenorphine (SRB) and buprenorphine after subcutaneous administration in dogs undergoing ovariohysterectomy. In a prospective, randomized, blinded design, 20 healthy adult female Beagle dogs underwent routine ovariohysterectomy and received multimodal analgesia consisting of meloxicam and one of two buprenorphine formulations. Dogs were randomly assigned to receive either SRB (0.2 mg/kg SC, once) or buprenorphine (0.02 mg/kg SC every 12 h for 3 d). Blinded observers assessed all dogs by using sedation scores, pain scores, temperature, HR, RR, and general wellbeing. Dogs were provided rescue analgesia with 0.02 mg/kg buprenorphine SC if the postoperative pain score exceeded a predetermined threshold. Blood samples were collected, and mass spectrometry was used to determine plasma buprenorphine concentrations. Data were analyzed with a linear mixed model and Tukey–Kramer multiple comparison. Age, body weight, anesthetic duration, surgical duration, sevoflurane concentration, and cardiorespiratory variables did not differ significantly between groups. Dogs in both formulation groups had comparable postoperative sedation and pain scores. One dog from each formulation group had breakthrough pain requiring rescue analgesia. Plasma buprenorphine concentrations remained above a hypothesized therapeutic concentration of 0.6 ng/mL for 136.0 ± 11.3 and 10.67 ± 0.84 h for SRB and buprenorphine, respectively. Based on the results of this study, multimodal analgesic regimens consisting of meloxicam and either buprenorphine or SRB are equally efficacious in managing pain associated with an ovariohysterectomy and show comparable side effects. PMID:25255072

  2. A preliminary study comparing methadone and buprenorphine in patients with chronic pain and coexistent opioid addiction.

    Science.gov (United States)

    Neumann, Anne M; Blondell, Richard D; Jaanimägi, Urmo; Giambrone, Amanda K; Homish, Gregory G; Lozano, Jacqueline R; Kowalik, Urszula; Azadfard, Mohammadreza

    2013-01-01

    Patients with opioid addiction who receive prescription opioids for treatment of nonmalignant chronic pain present a therapeutic challenge. Fifty-four participants with chronic pain and opioid addiction were randomized to receive methadone or buprenorphine/naloxone. At the 6-month follow-up examination, 26 (48.1%) participants who remained in the study noted a 12.75% reduction in pain (P = 0.043), and no participants in the methadone group compared to 5 in the buprenorphine group reported illicit opioid use (P = 0.039). Other differences between the two conditions were not found. Long-term, low-dose methadone or buprenorphine/naloxone treatment produced analgesia in participants with chronic pain and opioid addiction.

  3. Integrating Buprenorphine Into an Opioid Treatment Program: Tailoring Care for Patients With Opioid Use Disorders

    Science.gov (United States)

    Polydorou, Soteri; Ross, Stephen; Coleman, Peter; Duncan, Laura; Roxas, Nichole; Thomas, Anil; Mendoza, Sonia; Hansen, Helena

    2016-01-01

    Objectives This report identifies the institutional barriers to, and benefits of, buprenorphine maintenance treatment (BMT) integration in an established hospital-based opioid treatment program (OTP). Methods This case study presents the authors’ experiences at the clinic, hospital, and corporation levels during efforts to integrate BMT into a hospital-based OTP in New York City and a descriptive quantitative analysis of the characteristics of hospital outpatients treated with buprenorphine from 2006 to 2013 (N=735). Results Integration of BMT into an OTP offered patients the flexibility to transition between intensive structured care and primary care or outpatient psychiatry according to need. Main barriers encountered were regulations, clinical logistics of dispensing medications, internal cost and reimbursement issues, and professional and cultural resistance. Conclusions Buprenorphine integration offers a model for other OTPs to facilitate partnerships among primary care and mental health clinics to better serve diverse patients with varying clinical needs and with varying levels of social support. PMID:27745534

  4. Where Is Buprenorphine Dispensed to Treat Opioid Use Disorders? The Role of Private Offices, Opioid Treatment Programs, and Substance Abuse Treatment Facilities in Urban and Rural Counties.

    Science.gov (United States)

    Stein, Bradley D; Pacula, Rosalie Liccardo; Gordon, Adam J; Burns, Rachel M; Leslie, Douglas L; Sorbero, Mark J; Bauhoff, Sebastian; Mandell, Todd W; Dick, Andrew W

    2015-09-01

    Buprenorphine is an effective opioid dependence treatment that has expanded access to care since its 2002 approval, but it can only be prescribed by physicians waivered to treat a limited number of individuals. We examined the impact of 2006 legislation that increased waivered physician patient limits from 30 to 100 on buprenorphine use, and found that 100-patient-waivered physicians were significantly associated with growth in buprenorphine use, with no such relationship for 30-patient-waivered physicians. Policies relaxing patient limits may be more effective in increasing buprenorphine use than alternatives such as opening new substance abuse treatment facilities or increasing the overall number of waivered physicians. Opioid use disorders are a significant public health problem. In 2002, the FDA approved buprenorphine as an opioid use disorder treatment when prescribed by waivered physicians who were limited to treating 30 patients at a time. In 2006, federal legislation raised this number to 100 patients. Although federal legislators are considering increasing these limits further and expanding prescribing privileges to nonphysicians, little information is available regarding the impact of such changes on buprenorphine use. We therefore examined the impact of the 2006 legislation-as well as the association between urban and rural waivered physicians, opioid treatment programs, and substance abuse treatment facilities-on buprenorphine distributed per capita over the past decade. Using 2004-2011 state-level data on buprenorphine dispensed and county-level data on the number of buprenorphine-waivered physicians and substance abuse treatment facilities using buprenorphine, we estimated a multivariate ordinary least squares regression model with state fixed effects of a state's annual total buprenorphine dispensed per capita as a function of the state's number of buprenorphine providers. The amount of buprenorphine dispensed has been increasing at a greater rate

  5. Pharmacokinetic Profiles of Meloxicam and Sustained-release Buprenorphine in Prairie Dogs (Cynomys ludovicianus).

    Science.gov (United States)

    Cary, Cynthia D; Lukovsky-Akhsanov, Nicole L; Gallardo-Romero, Nadia F; Tansey, Cassandram M; Ostergaard, Sharon D; Taylor, Willie D; Morgan, Clint N; Powell, Nathaniel; Lathrop, George W; Hutson, Christina L

    2017-03-01

    In this study, we evaluated the pharmacokinetic profiles of meloxicam and sustained-release (SR) buprenorphine in prairie dogs. The 4 treatment groups were: low-dose meloxicam (0.2 mg/kg SC), high-dose meloxicam (4 mg/kg SC), low-dose buprenorphine SR (0.9 mg/kg SC), and high-dose buprenorphine SR (1.2 mg/kg SC). The highest plasma concentrations occurred within 4 h of administration for both meloxicam treatment groups. The therapeutic range of meloxicam in prairie dogs is currently unknown. However, as compared with the therapeutic range documented in other species (0.39 - 0.91 μg/mL), the mean plasma concentration of meloxicam fell below the minimal therapeutic range prior to 24 h in the low-dose group but remained above therapeutic levels for more than 72 h in the high-dose group. These findings suggest that the current meloxicam dosing guidelines may be subtherapeutic for prairie dogs. The highest mean plasma concentration for buprenorphine SR occurred at the 24-h time point (0.0098 μg/mL) in the low-dose group and at the 8-h time point (0.015 μg/mL) for the high-dose group. Both dosages of buprenorphine SR maintained likely plasma therapeutic levels (0.001 μg/mL, based on previous rodent studies) beyond 72 h. Given the small scale of the study and sample size, statistical analysis was not performed. The only adverse reactions in this study were mild erythematous reactions at injection sites for buprenorphine SR.

  6. Effects of acepromazine, butorphanol and buprenorphine on thermal and mechanical nociceptive thresholds in horses.

    Science.gov (United States)

    Love, E J; Taylor, P M; Murrell, J; Whay, H R

    2012-03-01

    To investigate the antinociceptive effects of buprenorphine administered in combination with acepromazine in horses and to establish an effective dose for use in a clinical environment. To evaluate the responses to thermal and mechanical stimulation following administration of 3 doses of buprenorphine compared to positive (butorphanol) and negative (glucose) controls. Observer blinded, randomised, crossover design using 6 Thoroughbred geldings (3-10 years, 500-560 kg). Thermal and mechanical nociceptive thresholds were measured 3 times at 15 min intervals. Horses then received acepromazine 0.05 mg/kg bwt with one of 5 treatments i.v.: 5% glucose (Glu), butorphanol 100 µg/kg bwt (But) buprenorphine 5 µg/kg bwt (Bup5), buprenorphine 7.5 µg/kg bwt (Bup7.5) and buprenorphine 10 µg/kg bwt (Bup10). Thresholds were measured 15, 30, 45, 60, 90, 120, 150, 180, 230 min, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 24 h post treatment administration. The 95% confidence intervals for threshold temperature (ΔT) for each horse were calculated and an antinociceptive effect defined as ΔT, which was higher than the upper limit of the confidence interval. Duration of thermal antinociception was analysed using a within-subjects ANOVA and peak mechanical thresholds with a general linear model with post hoc Tukey tests. Significance was set at Pbuprenorphine produced antinociception to a thermal stimulus for significantly longer than acepromazine and either butorphanol or glucose. This study suggests that buprenorphine has considerable potential as an analgesic in horses and should be examined further under clinical conditions and by investigation of the pharmacokinetic/pharmacodynamic profile. © 2011 EVJ Ltd.

  7. Neonatal outcomes and their relationship to maternal buprenorphine dose during pregnancy.

    Science.gov (United States)

    Jones, Hendrée E; Dengler, Erin; Garrison, Anna; O'Grady, Kevin E; Seashore, Carl; Horton, Evette; Andringa, Kim; Jansson, Lauren M; Thorp, John

    2014-01-01

    Buprenorphine pharmacotherapy for opioid-dependent pregnant women is associated with maternal and neonatal outcomes superior to untreated opioid dependence. However, the literature is inconsistent regarding the possible existence of a dose-response relationship between maternal buprenorphine dose and neonatal clinical outcomes. The present secondary analysis study (1) examined the relationship between maternal buprenorphine dose at delivery and neonatal abstinence syndrome (NAS) peak score, estimated gestational age at delivery, Apgar scores at 1 and 5 min, neonatal head circumference, length, and weight at birth, amount of morphine needed to treat NAS, duration of NAS treatment, and duration of neonatal hospital stay and (2) compared neonates who required pharmacotherapy for NAS to neonates who did not require such pharmacotherapy on these same outcomes, in 58 opioid-dependent pregnant women receiving buprenorphine as participants in a randomized clinical trial. (1) Analyses failed to provide evidence of a relationship between maternal buprenorphine dose at delivery and any of the 10 outcomes (all p-values>.48) and (2) significant mean differences between the untreated (n=31) and treated (n=27) for NAS groups were found for duration of neonatal hospital stay and NAS peak score (both p-values<.001). (1) Findings failed to support the existence of a dose-response relationship between maternal buprenorphine dose at delivery and any of 10 neonatal clinical outcomes, including NAS severity and (2) that infants treated for NAS had a higher mean NAS peak score and, spent a longer time in the hospital than did the group not treated for NAS is unsurprising. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Subcutaneous Implants of Buprenorphine-Cholesterol-Triglyceride Powder in Mice

    Directory of Open Access Journals (Sweden)

    L. DeTolla

    2014-01-01

    Full Text Available Subcutaneous drug implants are convenient systems for the long-term delivery of drugs in animals. Lipid carriers are logical tools because they generally allow for higher doses and low toxicity. The present study used an US Food and Drug Administration Target Animal Safety test system to evaluate the safety of a subcutaneous implant of a cholesterol-triglyceride-buprenorphine powder in 120 BALB/c mice. Mice were evaluated in 4- and 12-day trials with 1- and 5-fold doses of the intended 3 mg/kg dose of drug. One male mouse treated with three 3 mg/kg doses and surgery on days 0, 4, and 8 died on day 9. The cause of death was not determined. In the surviving 119 mice there was no evidence of skin reaction at the site of the implant. Compared to control animals treated with saline, weight measurements, clinical pathology, histopathology, and clinical observations were unremarkable. These results demonstrate that the lipid carrier is substantially safe. Cholesterol-triglyceride-drug powders may provide a valuable research tool for studies of analgesic and inflammatory drug implants in veterinary medicine.

  9. Illicit use of methadone and buprenorphine among adolescents and young adults in Sweden.

    Science.gov (United States)

    Richert, Torkel; Johnson, Björn

    2013-10-18

    Illicit use of methadone and buprenorphine has been described as a growing problem in Sweden in recent years, and has been associated with an increased drug-related mortality. Critics claim that the substances have become popular among adolescents and that they function as a gateway to heroin use. The aim of this study is to investigate, firstly, the extent to which illicit use of methadone and buprenorphine occurs among adolescents and young adults in Sweden, and secondly, at what stage in a user's drug career these substances tend to appear. The study is based on surveys and structured interviews on drug use among various populations of young people, in addition to qualitative interviews with 86 informants who, in their professional capacity, encounter adolescents or young adults who are using illicit drugs. Illicit use of methadone and buprenorphine is rare among young people in Sweden. According to high school surveys, less than 0.1% have tried these substances. Among young drug users in general, few have tried the substances, and there is nothing to indicate that they act as gateway drugs. Among adolescents and young adults with severe drug problems, however, the illicit use of methadone and buprenorphine is more common (54% in a compulsory care sample). These substances normally enter the drug career late, and few use them as their main drug of choice. Other prescription drugs, like benzodiazepines and tramadol, are used by adolescents to a far greater extent. Diversion and illicit use of methadone and buprenorphine is not seen as a serious problem by the professionals interviewed. A general view is that the substances are mainly used by people with a heroin or polydrug addiction, often for "self-medication" purposes. However, several informants express concern that methadone and buprenorphine may cause fatalities among young drug users without an opioid tolerance. Illicit use of methadone and buprenorphine among young drug users is not a widespread problem

  10. Tramadol versus buprenorphine for the management of acute heroin withdrawal: a retrospective matched cohort controlled study.

    Science.gov (United States)

    Threlkeld, Melinda; Parran, Theodore V; Adelman, Christopher A; Grey, Scott F; Yu, Jaehak

    2006-01-01

    Many medications have been used over the past thirty years for the treatment of opioid withdrawal, including propoxyphene, methadone, clonidine, parenteral buprenorphine, and, more recently, sublingual buprenorphine. Each has been found to have clinical strengths and limitations. Tramadol is a centrally acting synthetic analgesic with opiate activity primarily due to the binding of a metabolite to the micro receptor. Despite this micro receptor activity, tramadol appears to have low abuse potential and is a non-scheduled analgesic. The pharmacologic profile of tramadol makes it a candidate for opiate withdrawal treatment. A chart review was undertaken to retrospectively compare treatment outcomes of heroin-dependent patients when detoxified with parenteral buprenorphine (1996-1997) versus tramadol (1999-2000). Inclusion criteria for this study were heroin as drug of choice, current opioid physical dependence (ie, withdrawal symptoms), no current abuse of oral opioid analgesics, and no alcohol or benzodiazepine withdrawal symptoms. Patient cases that met inclusion criteria were group-matched between buprenorphine and tramadol on the basis of age, sex, and amount of heroin used (bags/day). Charts were audited for patient demographics, daily heroin use at admission, withdrawal symptoms, and discharge status. In total, 129 patient charts were reviewed, and 115 met all inclusion criteria and were group-matched (45 patients in the buprenorphine group, seventy in the tramadol group). There were no differences in demographics between the two groups of patients. Fifty-six percent of the buprenorphine group and 71% of the tramadol group completed detoxification; tramadol-treated patients had significantly higher average withdrawal symptoms when compared to the buprenorphine group and a greater reduction in withdrawal symptoms over time. Finally, the number of side effects was small and did not differ between the groups. The results of this study are consistent with previous

  11. Enhancement of tolerance development to morphine in rats prenatally exposed to morphine, methadone, and buprenorphine

    Directory of Open Access Journals (Sweden)

    Ho Ing-Kang

    2010-06-01

    Full Text Available Abstract Background Abuse of addictive substances is a serious problem that has a significant impact on areas such as health, the economy, and public safety. Heroin use among young women of reproductive age has drawn much attention around the world. However, there is a lack of information on effects of prenatal exposure to opioids on their offspring. In this study, an animal model was established to study effects of prenatal exposure to opioids on offspring. Methods Female pregnant Sprague-Dawley rats were sub-grouped to receive (1 vehicle, (2 2-4 mg/kg morphine (1 mg/kg increment per week, (3 7 mg/kg methadone, and (4 3 mg/kg buprenorphine, subcutaneously, once or twice a day from E3 to E20. The experiments were conducted on animals 8-12 weeks old and with body weight between 250 and 350 g. Results Results showed that prenatal exposure to buprenorphine caused higher mortality than other tested substance groups. Although we observed a significantly lower increase in body weight in all of the opioid-administered dams, the birth weight of the offspring was not altered in all treated groups. Moreover, no obvious behavioral abnormality or body-weight difference was noted during the growing period (8-12 weeks in all offspring. When the male offspring received morphine injection twice a day for 4 days, the prenatally opioid-exposed rats more quickly developed a tolerance to morphine (as shown by the tail-flick tests, most notably the prenatally buprenorphine-exposed offspring. However, the tolerance development to methadone or buprenorphine was not different in offspring exposed prenatally to methadone or buprenorphine, respectively, when compared with that of the vehicle controlled group. Similar results were also obtained in the female animals. Conclusions Animals prenatally exposed to morphine, methadone, or buprenorphine developed tolerance to morphine faster than their controlled mates. In our animal model, prenatal exposure to buprenorphine also

  12. Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model

    DEFF Research Database (Denmark)

    Ravn, Pernille; Secher, EL; Skram, U

    2013-01-01

    Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than μ-opioid receptor agonists. The primary outcome of this study was therefore...... to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending...

  13. Low-dose naloxone provides an abuse-deterrent effect to buprenorphine

    Directory of Open Access Journals (Sweden)

    Webster LR

    2015-11-01

    Full Text Available Lynn R Webster,1 Michael D Smith,1 Cemal Unal,2 Andrew Finn3 1PRA Health Sciences, Salt Lake City, UT, USA; 2Biometrical Solutions LLC, Raleigh, NC, USA; 3BioDelivery Sciences International, Inc., Raleigh, NC, USA Abstract: In developmental research, plasma buprenorphine concentrations comparable to a 2 mg buprenorphine–naloxone (BN sublingual tablet have been achieved with a 0.75 mg dose of BN buccal film, a small, bioerodible polymer film for application to mucosal membranes. This was a randomized, double-blind, placebo-controlled, single-dose, four-period crossover study in opioid-dependent subjects with chronic pain receiving >100 mg oral morphine equivalents daily who experienced withdrawal following a naloxone challenge dose. The objective of the study was to determine if intravenous (IV naloxone doses of 0.1 and 0.2 mg would produce a withdrawal response when coadministered with a 0.75 mg IV dose of buprenorphine. Fifteen subjects receiving 90–1,260 mg oral morphine equivalents per day enrolled and completed the study. Precipitated withdrawal occurred in 13% (2/15 of placebo-treated subjects and 47% (7/15 of buprenorphine-treated subjects. When combined with the 0.75 mg dose of buprenorphine, a 0.1 mg dose of naloxone increased the incidence of precipitated withdrawal to 60%, and a 0.2 mg dose of naloxone increased the incidence to 73%. By 15 minutes postdose, the mean change in Clinical Opioid Withdrawal Scale (COWS score from predose was 3.0 for placebo, 6.9 for buprenorphine, 9.8 for BN 0.1 mg, and 12.4 for BN 0.2 mg. The mean COWS score with each active treatment was significantly greater than placebo (P<0.001, and the mean COWS score for each of the naloxone-containing treatments was significantly greater than for buprenorphine alone (P<0.001. Naloxone doses as low as 0.1 mg added an abuse-deterrent effect to a 0.75 mg IV dose of buprenorphine. Keywords: opioid dependence, withdrawal symptoms, abuse-deterrent, buprenorphine

  14. [Necrosis of the glans penis: a complication of an injection of buprenorphin in a opioid abuser].

    Science.gov (United States)

    Hornez, E; Laroche, J; Monchal, T; Bourgouin, S; Riviere, P; Fournier, R; Dantzer, E

    2010-04-01

    Necrosis of the penis glans is commonly described after circumcision or strangulation. We report the case of a patient, opioid abuser, who presented an isolated glans necrosis after an injection of buprenorphin. The buprenorphin (Subutex) is a sublingual partial mu-opioid agonist used for the treatment of heroin dependance. Its intravenous or subcutaneous abuse is associated with local infection. The patient require a surgical intervention. After the failure of a mucosal graft, a soft skin graft was done. Copyright 2009 Elsevier Masson SAS. All rights reserved.

  15. Public sector low threshold office-based buprenorphine treatment: outcomes at year 7.

    Science.gov (United States)

    Bhatraju, Elenore Patterson; Grossman, Ellie; Tofighi, Babak; McNeely, Jennifer; DiRocco, Danae; Flannery, Mara; Garment, Ann; Goldfeld, Keith; Gourevitch, Marc N; Lee, Joshua D

    2017-02-28

    Buprenorphine maintenance for opioid dependence remains of limited availability among underserved populations, despite increases in US opioid misuse and overdose deaths. Low threshold primary care treatment models including the use of unobserved, "home," buprenorphine induction may simplify initiation of care and improve access. Unobserved induction and long-term treatment outcomes have not been reported recently among large, naturalistic cohorts treated in low threshold safety net primary care settings. This prospective clinical registry cohort design estimated rates of induction-related adverse events, treatment retention, and urine opioid results for opioid dependent adults offered buprenorphine maintenance in a New York City public hospital primary care office-based practice from 2006 to 2013. This clinic relied on typical ambulatory care individual provider-patient visits, prescribed unobserved induction exclusively, saw patients no more than weekly, and did not require additional psychosocial treatment. Unobserved induction consisted of an in-person screening and diagnostic visit followed by a 1-week buprenorphine written prescription, with pamphlet, and telephone support. Primary outcomes analyzed were rates of induction-related adverse events (AE), week 1 drop-out, and long-term treatment retention. Factors associated with treatment retention were examined using a Cox proportional hazard model among inductions and all patients. Secondary outcomes included overall clinic retention, buprenorphine dosages, and urine sample results. Of the 485 total patients in our registry, 306 were inducted, and 179 were transfers already on buprenorphine. Post-induction (n = 306), week 1 drop-out was 17%. Rates of any induction-related AE were 12%; serious adverse events, 0%; precipitated withdrawal, 3%; prolonged withdrawal, 4%. Treatment retention was a median 38 weeks (range 0-320) for inductions, compared to 110 (0-354) weeks for transfers and 57 for the entire clinic

  16. Pharmacokinetics of a Sustained Release Formulation of Buprenorphine After Intramuscular and Subcutaneous Administration to American Kestrels ( Falco sparverius ).

    Science.gov (United States)

    Guzman, David Sanchez-Migallon; Knych, Heather K; Olsen, Glenn H; Paul-Murphy, Joanne R

    2017-06-01

    Previous studies have validated the clinical use of opioids with μ-receptor affinities for pain management in raptors. Buprenorphine appears to have a longer duration of action and minimal adverse effects when compared to other opioids in American kestrels ( Falco sparverius ). To determine the pharmacokinetics of a sustained release formulation of buprenorphine in kestrels, we administered a commercially available product (Buprenorphine SR-LAB; Wildlife Pharmaceuticals, Windsor, CO, USA) intramuscularly and subcutaneously to adult kestrels in a partial-crossover experimental design study. A total of 12 birds (6 males and 6 females) were assigned randomly to 3 groups of 4 birds each. A single dose of Buprenorphine SR-LAB (1.8 mg/kg) was administered intramuscularly (IM), and blood samples were collected at 0.25, 3, and 24 hours (n = 4); 1, 6, and 48 hours (n = 4); and 2, 12, and 72 hours (n = 4) after drug administration. Plasma buprenorphine concentrations were measured by tandem liquid chromatography-mass spectrometry. Pharmacokinetic parameters were determined by use of least squares linear regression and noncompartmental analysis of naïve pooled data. After 1 year, the same dose of buprenorphine was administered subcutaneously (SC) to 12 birds divided into 3 groups as previously, and blood samples were collected at the same times after drug administration. Maximum plasma buprenorphine concentration was measured at 15 minutes after IM and SC administration. Mean plasma buprenorphine concentrations were >1 ng/mL for 48 hours after IM and SC administration. The elimination half-life was 13.5 and 11.1 hours for IM and SC administration, respectively. Depending on the severity and type of pain, adjunctive therapy, and the individual response, Buprenorphine SR-LAB administered at 1.8 mg/kg IM or SC to American kestrels would require administration every 12 to 72 hours to manage pain. Further pharmacodynamic and clinical evaluations are warranted in kestrels and

  17. Buprenorphine for human immunodeficiency virus/hepatitis C virus-coinfected patients: does it serve as a bridge to hepatitis C virus therapy?

    Science.gov (United States)

    Taylor, Lynn E; Maynard, Michaela A; Friedmann, Peter D; Macleod, Cynthia J; Rich, Josiah D; Flanigan, Timothy P; Sylvestre, Diana L

    2012-09-01

    Buprenorphine is associated with enhanced human immunodeficiency virus (HIV) treatment outcomes including increased antiretroviral therapy initiation rates, adherence, and CD4 cell counts among HIV-infected opioid-dependent individuals. Buprenorphine facilitates hepatitis C virus (HCV) treatment in opioid-dependent patients with HCV monoinfection. Less is known about buprenorphine's role in HIV/HCV coinfection. We conducted a retrospective chart review to evaluate HCV care for HIV-infected buprenorphine patients in the first 4 years of buprenorphine's integration into a Rhode Island HIV clinic. Sixty-one patients initiated buprenorphine. All had HCV antibody testing; 57 (93%) were antibody-positive. All antibody-positive patients underwent HCV RNA testing; 48 (84%) were RNA-positive. Of these, 15 (31%) were not referred to HCV care. Among chronically infected patients, 3 received HCV treatment after buprenorphine; all had cirrhosis and none achieved viral eradication. At buprenorphine induction, most patients had inadequately controlled HIV infection, with detectable HIV RNA (59%) or CD4 cell count less than or equal to 350/μL (38%). Buprenorphine has shown limited success to date as a bridge to HCV treatment within an HIV clinic. Buprenorphine's stabilization of opioid dependence and HIV disease may permit the use of HCV therapy over time.

  18. Effects of regulation on methadone and buprenorphine provision in the wake of Hurricane Sandy.

    Science.gov (United States)

    McClure, Bridget; Mendoza, Sonia; Duncan, Laura; Rotrosen, John; Hansen, Helena

    2014-10-01

    Hurricane Sandy led to the closing of many major New York City public hospitals including their substance abuse clinics and methadone programs, and the displacement or relocation of thousands of opioid-dependent patients from treatment. The disaster provided a natural experiment that revealed the relative strengths and weaknesses of methadone treatment in comparison to physician office-based buprenorphine treatment for opioid dependence, two modalities of opioid maintenance with markedly different regulatory requirements and institutional procedures. To assess these two modalities of treatment under emergency conditions, semi-structured interviews about barriers to and facilitators of continuity of care for methadone and buprenorphine patients were conducted with 50 providers of opioid maintenance treatment. Major findings included that methadone programs presented more regulatory barriers for providers, difficulty with dose verification due to impaired communication, and an over reliance on emergency room dosing leading to unsafe or suboptimal dosing. Buprenorphine treatment presented fewer regulatory barriers, but buprenorphine providers had little to no cross-coverage options compared to methadone providers, who could refer to alternate methadone programs. The findings point to the need for well-defined emergency procedures with flexibility around regulations, the need for a central registry with patient dose information, as well as stronger professional networks and cross-coverage procedures. These interventions would improve day-to-day services for opioid-maintained patients as well as services under emergency conditions.

  19. Mobile phone use patterns and preferences in safety net office-based buprenorphine patients.

    Science.gov (United States)

    Tofighi, Babak; Grossman, Ellie; Buirkle, Emily; McNeely, Jennifer; Gourevitch, Marc; Lee, Joshua D

    2015-01-01

    Integrating mobile phone technologies in addiction treatment is of increasing importance and may optimize patient engagement with their care and enhance the delivery of existing treatment strategies. Few studies have evaluated mobile phone and text message (TM) use patterns in persons enrolled in addiction treatment, and none have assessed the use in safety net, office-based buprenorphine practices. A 28-item, quantitative and qualitative semistructured survey was administered to opiate-dependent adults in an urban, publicly funded, office-based buprenorphine program. Survey domains included demographic characteristics, mobile phone and TM use patterns, and preferences pertaining to their recovery. Surveyors approached 73 of the 155 eligible subjects (47%); 71 respondents completed the survey. Nearly all participants reported mobile phone ownership (93%) and TM use (93%), and most reported "very much" or "somewhat" comfort sending TM (79%). Text message contact with 12-step group sponsors, friends, family members, and counselors was also described (32%). Nearly all preferred having their providers' mobile phone number (94%), and alerting the clinic via TM in the event of a potential relapse to receive both supportive TM and a phone call from their buprenorphine provider was also well received (62%). Mobile phone and TM use patterns and preferences among this sample of office-based buprenorphine participants highlight the potential of adopting patient-centered mobile phone-based interventions in this treatment setting.

  20. Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers.

    Science.gov (United States)

    Fischer, Andreas; Jönsson, Martin; Hjelmström, Peter

    2015-01-01

    Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery. To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability. Dry mixing techniques were employed to produce a small and fast dissolving buprenorphine/naloxone sublingual tablet formulation, OX219 (Zubsolv®), using sucralose and menthol as sweetener and flavor to mask the bitter taste of the active ingredients. Two cross-over studies were performed in healthy volunteers to evaluate pharmacokinetics, dissolve time and acceptability of OX219 5.7/1.4 mg tablets compared to the commercially available buprenorphine/naloxone formulations Suboxone® tablets and films (8/2 mg). Buprenorphine exposure was equivalent in OX219 and Suboxone tablets. Sublingual dissolve times were significantly shorter for OX219 than for Suboxone tablets and were similar to Suboxone films. The OX219 formulation received significantly higher subjective ratings for taste and overall acceptability than both Suboxone formulations. OX219 was preferred over Suboxone tablet and film formulations by 77.4% and 88.9% of subjects, respectively. A sublingual tablet formulation with an improved acceptability has been successfully developed.

  1. Buprenorphine Transdermal System for Opioid Therapy in Patients with Chronic Low Back Pain

    Directory of Open Access Journals (Sweden)

    Allan Gordon

    2010-01-01

    Full Text Available OBJECTIVE: The present randomized, double-blinded, crossover study compared the efficacy and safety of a seven-day buprenorphine transdermal system (BTDS and placebo in patients with low back pain of moderate or greater severity for at least six weeks.

  2. Pharmacokinetics of buprenorphine following intravenous and intramuscular administration in male rhesus macaques (Macaca mulatta)

    Science.gov (United States)

    Kelly, Kristi R.; Pypendop, Bruno H.; Christe, Kari L.

    2014-01-01

    This study reports the pharmacokinetics of buprenorphine in conscious rhesus macaques (Macaca mulatta) after intravenous (IV) and intramuscular (IM) administration. Four healthy, opioid-naïve, socially-housed, adult male macaques were used. Buprenorphine (0.03 mg/kg) was administered intravenously as a bolus or intramuscularly on separate occasions. Blood samples were collected prior to, and up to 24 h, post-administration. Serum buprenorphine concentrations were analyzed with liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed with commercially available software. Mean residence time in the IV study as compared to the IM study was 177 (159–189) minutes vs. 185 (174–214) minutes, respectively [median (range)]. In the IV study, concentration back extrapolated to time zero was found to be 33.0 (16.8–57.0) ng/mL [median (range)]. On the other hand, the maximum serum concentration found in the IM study was 11.8 (6.30–14.8) ng/mL [median (range)]. Rhesus macaques maintained concentrations greater than 0.10 ng/mL for over 24 h in the IV study and over 12 h in the IM study. Bioavailability was found to be 68.1 (59.3–71.2)% [median (range)]. No significant adverse effects were observed in the monkeys at the 0.03 mg/kg dose of buprenorphine during either study. PMID:24666428

  3. A comparison of subarachnoid buprenorphine or xylazine as an adjunct to lidocaine for analgesia in goats.

    Science.gov (United States)

    Staffieri, Francesco; Driessen, Bernd; Lacitignola, Luca; Crovace, Antonio

    2009-09-01

    To test the hypothesis that subarachnoid administration of buprenorphine and lidocaine provides more intense and longer lasting perioperative analgesia with less side effects than xylazine and lidocaine in goats. Randomized, blinded, controlled study. STUDY ANIMALS: Ten healthy female goats randomly assigned to two groups of five animals each. After sedation with acepromazine (0.1 mg kg(-1)) intravenously (i.v.), lidocaine 2% (0.1 mL kg(-1)) combined with either xylazine (0.05 mg kg(-1); Group X) or buprenorphine (0.005 mg kg(-1); Group B) were injected intrathecally at the lumbo-sacral junction prior to stifle surgery. Electrocardiogram, heart rate, direct systolic, mean, and diastolic arterial blood pressures, rectal temperature and arterial blood gases were recorded as were post-operative sedation and pain scores using a visual analogue and numeric rating scale, respectively. Data were analyzed with one-way ANOVA for repeated measures, one-way anova, Friedman's and Kruskal-Wallis tests as necessary (p buprenorphine and lidocaine produced more profound and longer lasting analgesia with less sedation and hemodynamic and respiratory impairment than xylazine with lidocaine. In these goats undergoing hind limb surgery, subarachnoid buprenorphine/lidocaine offered more intense and longer lasting analgesia than a xylazine/lidocaine combination, with less sedation and impairment of cardiopulmonary function.

  4. Synthesis of high-specific activity [15,16-{sup 3}H{sub 2}]buprenorphine

    Energy Technology Data Exchange (ETDEWEB)

    Oetvoes, F.; Toth, G. [Hungarian Academy of Sciences, Szeged (Hungary). Isotope Lab.; Hosztafi, S.; Simon, C. [Alkaloida Chemical Factory Ltd., Tiszavasvari (Hungary)

    1995-01-01

    Tritium labelling of buprenorphine, a mixed agonist-antagonist opioid ligand, was performed with a specific activity of 2.35 TBq/mmol (63.6 Ci/mmol) starting with 15,16-didehydrobuprenorphine. Labels at positions 15 and 16 of the morphine skeleton proved to be sufficiently stable under strong acidic or basic conditions. (Author).

  5. Developing and Implementing a New Prison-Based Buprenorphine Treatment Program

    Science.gov (United States)

    Kinlock, Timothy W.; Gordon, Michael S.; Schwartz, Robert P.; Fitzgerald, Terrence T.

    2010-01-01

    Research suggests that buprenorphine treatment may be a promising intervention for incarcerated individuals with heroin addiction histories. However, its implementation varies from corrections-based methadone because of unique challenges regarding dosing, administration, and regulation. Describing the first randomized clinical trial of…

  6. A randomized clinical trial of buprenorphine for prisoners: Findings at 12-months post-release.

    Science.gov (United States)

    Gordon, Michael S; Kinlock, Timothy W; Schwartz, Robert P; O'Grady, Kevin E; Fitzgerald, Terrence T; Vocci, Frank J

    2017-03-01

    This study examined whether starting buprenorphine treatment prior to prison and after release from prison would be associated with better drug treatment outcomes and whether males and females responded differently to the combination of in-prison treatment and post-release service setting. Study design was a 2 (In-Prison Treatment: Condition: Buprenorphine Treatment: vs. Counseling Only)×2 [Post-Release Service Setting Condition: Opioid Treatment: Program (OTP) vs. Community Health Center (CHC)]×2 (Gender) factorial design. The trial was conducted between September 2008 and July 2012. Follow-up assessments were completed in 2014. Participants were recruited from two Baltimore pre-release prisons (one for men and one for women). Adult pre-release prisoners who were heroin-dependent during the year prior to incarceration were eligible. Post-release assessments were conducted at 1, 3, 6, and 12-month following prison release. Participants (N=211) in the in-prison treatment condition effect had a higher mean number of days of community buprenorphine treatment compared to the condition in which participants initiated medication after release (P=0.005). However, there were no statistically significant hypothesized effects for the in-prison treatment condition in terms of: days of heroin use and crime, and opioid and cocaine positive urine screening test results (all Ps>0.14) and no statistically significant hypothesized gender effects (all Ps>0.18). Although initiating buprenorphine treatment in prison compared to after-release was associated with more days receiving buprenorphine treatment in the designated community treatment program during the 12-months post-release assessment, it was not associated with superior outcomes in terms of heroin and cocaine use and criminal behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. [Demand for emergency department care for vertebral fractures treated with transdermal buprenorphine vs. other analgesics].

    Science.gov (United States)

    Guillén Astete, Carlos A; Boteanu, Alina; Luque Alarcón, Mónica; Carballo Cardona, César; Roldán Moll, Fernando; Fernández Pérez, Cristina

    2016-01-01

    To compare the results of emergency department management of spinal pain from vertebral fractures (in terms of revisits, adverse effects at 90 days, or need for hospitalization because of poor pain control at 6 months) in patients treated with transdermal buprenorphine or another analgesic. Retrospective observational study of cohorts in an emergency department database compiled prospectively over a period of 18 months. We included all patients over the age of 60 with a radiologic diagnosis of vertebral fracture or compression causing pain for more than 3 months. Records were stratified according to the World Health Organization (WHO) analgesic scale, which was used when the patients were treated. Variables related to effectiveness were revisits at 1 month, time between visits in days, and the need for hospitalization. A total of 180 patients were included; 39 were treated with drugs on the first step of the WHO's analgesic ladder, 74 with second-step drugs (mainly tramadol), and 67 with transdermal buprenorphine, a third-step drug. Half the patients treated with buprenorphine had revisited at 50 days or later (interquartile range [IQR, 41-60 days); half those treated with first-step analgesics had revisited by 19 days IQR, 10-37 days), and half those on second-step drugs had revisited by 28 days (IQR, 21-53 days) (P<.001). After adjustment for other variables, patients treated with first-step drugs revisited 4.19-fold more (95% CI, 2.57-6.80; P<.001) and those treated with second-step drugs revisited 1.91-fold more (95% CI, 1.22-2.99; P=.005) more than patients treated with transdermal buprenorphine. Transdermal buprenorphine used to manage spinal pain seems to significantly reduce the need for revisits in comparison with treatments with first- or second-step analgesics.

  8. Pharmacokinetic and pharmacodynamic modelling of intravenous, intramuscular and subcutaneous buprenorphine in conscious cats.

    Science.gov (United States)

    Steagall, Paulo V M; Pelligand, Ludovic; Giordano, Tatiana; Auberger, Christophe; Sear, John W; Luna, Stelio P L; Taylor, Polly M

    2013-01-01

    To describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (SC) buprenorphine in cats. Randomized, prospective, blinded, three period crossover experiment. Six healthy adult cats weighing 4.1±0.5 kg. Buprenorphine (0.02 mg kg(-1)) was administered i.v., i.m. or s.c.. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (pbuprenorphine concentration-time data decreased curvilinearly. S.c. PK could not be modeled due to erratic absorption and disposition. I.v. buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t(1/2) k(e0)=47.4 minutes) and receptor binding (k(on)=0.011 mL ng(-1) minute(-1)). Persistence of thermal antinociception was due to slow receptor dissociation (t(1/2) k(off)=18.2 minutes). I.v. and i.m. data followed classical disposition and elimination in most cats. Plasma concentrations after i.v. administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the i.v. route should be preferred over the i.m. and s.c. routes when buprenorphine is administered to cats. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  9. Comparison of toxicity associated with nonmedical use of benzodiazepines with buprenorphine or methadone.

    Science.gov (United States)

    Lee, Samantha C; Klein-Schwartz, Wendy; Doyon, Suzanne; Welsh, Christopher

    2014-05-01

    Polysubstance use is prevalent in individuals using buprenorphine or methadone nonmedically, with benzodiazepines being a common co-ingestant. The objective of this study was to compare the severity of buprenorphine and methadone toxicity with concomitant use of benzodiazepines. A retrospective analysis of buprenorphine and methadone cases from November 1, 2002 to December 31, 2010 reported to the American Association of Poison Control Centers' National Poison Data System (NPDS) was conducted. age ≥ 18 years, nonmedical use of methadone with benzodiazepines (methadone-BZD) or buprenorphine with benzodiazepines (BUP-BZD), and case followed to a documented outcome. Cases with co-ingestants other than benzodiazepines were excluded. Clinical effects, treatments, disposition and final medical outcomes were evaluated. There were 692 methadone-BZD cases and 72 BUP-BZD cases. Clinical effects in methadone-BZD and BUP-BZD groups were lethargy (71.1%, 59.7%), respiratory depression (29.0%, 15.3%), coma (22.4%, 5.6%), respiratory arrest (4.5%, 0), hypotension (11.8%, 2.8%) and cardiac arrest (1.9%, 0), respectively. Patients in the methadone-BZD group were four-times more likely to receive naloxone (60.4% vs 15.3%) or be intubated (16.3% vs 4.2%) than in the BUP-BZD group. Hospitalization rates were highest for methadone-BZD patients with 67.3% receiving medical admissions compared to 43.3% of BUP-BZD patients. Outcomes were more serious for methadone-BZD cases (pbenzodiazepines with methadone is associated with higher hospitalization rates, greater ICU utilization rates and considerably worse medical outcomes when compared to nonmedical use of benzodiazepines with buprenorphine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Adams Clive E

    2007-01-01

    Full Text Available Abstract Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods Open label randomised controlled trial in NHS Primary Care (General Practices, Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. Results Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35–0.96, p = 0.065. A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33–3.21, p = 0.028. People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96–2.52 and six months post detoxification (7 vs 3, RR 1.45 CI 0.84–2.49. Conclusion Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens.

  11. Pharmacokinetics and Paw Withdrawal Pressure in Female Guinea Pigs (Cavia porcellus) Treated with Sustained-Release Buprenorphine and Buprenorphine Hydrochloride.

    Science.gov (United States)

    Smith, Brian J; Wegenast, Daniel J; Hansen, Ryan J; Hess, Ann M; Kendall, Lon V

    2016-11-01

    Providing appropriate analgesia is essential in minimizing pain and maintaining optimal animal care and welfare in laboratory animals. Guinea pigs are common animal models in biomedical research, often requiring analgesic support. Here we evaluated the pharmacokinetics and efficacy of a sustained-release formulation of buprenorphine (Bup-SR) in this species. Guinea pigs (n = 7 each group) received either Bup-HCl (0.05 mg/kg BID for 3 d) or Bup-SR (0.3 mg/kg once). Plasma collection and measurement of paw-withdrawal pressure (PWP) was conducted at 0, 1, 3, 6, 12, 26, 48, and 72 h after treatment. Plasma levels of Bup-HCl peaked at 2331 pg/mL at 1 h after administration and declined to 165 pg/mL by 12 h. Plasma concentrations of Bup-SR peaked at 1344 pg/mL at 26 h after administration and declined to 429 pg/mL by 48 h. The PWP of the Bup-HCltreated guinea pigs peaked at 674 g at 1 h and declined to 402 g at 6 h, whereas that of Bup-SRtreated guinea pigs at 1 h was 361 g, 555 g at 6 h (significantly higher than that after Bup-HCl), and peaked at 680 g at 12 h. The PWP of both treatments was similar from 24 to 72 h and ranged from 348 to 450 g. The plasma concentration and PWP showed good correlation. These results suggest that Bup-SR provides consistent analgesia equivalent to that of Bup-HCl for a prolonged period of time and that Bup-SR is an alternative method of analgesia in guinea pigs.

  12. Effects of voluntarily-ingested buprenorphine on plasma corticosterone levels, body weight, water intake, and behaviour in permanently catheterised rats

    DEFF Research Database (Denmark)

    Goldkuhl, Renée; Hau, Jann; Abelson, Klas

    2010-01-01

    This study investigated the peri- and postoperative effect of pre-emptive analgesia through voluntary ingestion of buprenorphine in Nutella, in male Sprague-Dawley rats. An arterial catheter was inserted and the rats were connected to an automated blood sampling device (AccuSampler). Blood samples...... were drawn up to 18 h after surgery and the plasma concentrations of corticosterone were quantified. Postoperative changes in water intake and body weight were recorded, and the behaviour of the rats was analysed during two 30-min periods. Pre-emptive oral buprenorphine treatment reduced the plasma...... corticosterone levels in the postoperative period, compared to controls treated with local anaesthetics. Buprenorphine-treated rats consumed more water and maintained body weight better. Behavioural observations indicated that buprenorphine changed the behaviour in non-operated rats but there was no difference...

  13. Buprenorphine-Mediated Transition from Opioid Agonist to Antagonist Treatment: State of the Art and New Perspectives

    Science.gov (United States)

    Mannelli, Paolo; Peindl, Kathleen S.; Lee, Tong; Bhatia, Kamal S.; Wu, Li-Tzy

    2012-01-01

    Constant refinement of opioid dependence (OD) therapies is a condition to promote treatment access and delivery. Among other applications, the partial opioid agonist buprenorphine has been studied to improve evidence-based interventions for the transfer of patients from opioid agonist to antagonist medications. This paper summarizes PubMed-searched clinical investigations and conference papers on the transition from methadone maintenance to buprenorphine and from buprenorphine to naltrexone, discussing challenges and advances. The majority of the 26 studies we examined were uncontrolled investigations. Many small clinical trials have demonstrated the feasibility of in- or outpatient transfer to buprenorphine from low to moderate methadone doses (up to 60–70 mg). Results on the conversion from higher methadone doses, on the other hand, indicate significant withdrawal discomfort, and need for ancillary medications and inpatient treatment. Tapering high methadone doses before the transfer to buprenorphine is not without discomfort and the risk of relapse. The transition buprenorphine-naltrexone has been explored in several pilot studies, and a number of treatment methods to reduce withdrawal intensity warrant further investigation, including the co-administration of buprenorphine and naltrexone. Outpatient transfer protocols using buprenorphine, and direct comparisons with other modalities of transitioning from opioid agonist to antagonist medications are limited. Given its potential salience, the information gathered should be used in larger clinical trials on short and long-term outcomes of opioid agonist-antagonist transition treatments. Future studies should also test new pharmacological mechanisms to help reduce physical dependence, and identify individualized approaches, including the use of pharmacogenetics and long-acting opioid agonist and antagonist formulations. PMID:22280332

  14. Patient Perspectives on Buprenorphine/Naloxone: A Qualitative Study of Retention During the Starting Treatment with Agonist Replacement Therapies (START) Study

    OpenAIRE

    Teruya, Cheryl; Schwartz, Robert P.; Mitchell, Shannon Gwin; Hasson, Albert L.; Thomas, Christie; Buoncristiani, Samantha H.; Hser, Yih-Ing; Wiest, Katharina; Cohen, Allan J.; Glick, Naomi; Jacobs, Petra; McLaughlin, Paul; Ling, Walter

    2014-01-01

    This study examines the barriers and facilitators of retention among patients receiving buprenorphine/naloxone at eight community-based opioid treatment programs across the United States. Participants (n=105) were recruited up to three-and-a-half years after having participated in a randomized clinical trial comparing the effect of buprenorphine/naloxone and methadone on liver function. Semi-structured interviews were conducted with 67 patients provided with buprenorphine/naloxone who had ter...

  15. Interpretation of urine drug testing results in patients using transdermal buprenorphine preparations for the treatment of chronic noncancer pain.

    Science.gov (United States)

    Markman, John D; Barbosa, William A; Gewandter, Jennifer S; Frazer, Maria; Rast, Shirley; Dugan, Michelle; Nandigam, Kiran; Villareal, Armando; Kwong, Tai C

    2015-06-01

    To determine whether the prevailing liquid chromatography and tandem mass spectroscopy assay (LC-MS/MS) assay designed to monitor buprenorphine compliance of the sublingual formulation used in the substance abuse treatment setting can be extrapolated to the transdermal formulation used in the chronic pain treatment setting, which is 1000-fold less concentrated. Retrospective chart review. Self-reported compliant patients using the transdermal or sublingual formulations of buprenorhphine. Transdermal patch application was also visually confirmed during clinic visits. Urine drug test results from a LC-MS/MS were compared between samples from transdermal and sublingual patients. While all sublingual patients tested positive for at least one metabolite of buprenorphine, only 69% of the transdermal patients did so. In addition, the most abundant metabolite in the transdermal patients was buprenorphine-glucuronide, as compared with norbuprenorphine-glucuronide in sublingual patients. These data suggest that currently available urine drug tests for buprenorphine, including the more expensive LC-MS/MS based assays, may not be sufficiently sensitive to detect the metabolites from transdermal buprenorphine patients. This study highlights the need to evaluate the value and sensitivity of urine drug tests given the wide range of buprenorphine dosing in clinical practice. These results underscore the need for additional cost benefit analyses comparing different confirmatory drug testing techniques including many commercially available drug testing options. © 2014 Wiley Periodicals, Inc. Wiley Periodicals, Inc.

  16. Notes from the Field: Pediatric Emergency Department Visits for Buprenorphine/Naloxone Ingestion - United States, 2008-2015.

    Science.gov (United States)

    Budnitz, Daniel S; Lovegrove, Maribeth C; Sapiano, Mathew R P; Mathew, Justin; Kegler, Scott R; Geller, Andrew I; Hampp, Christian

    2016-10-21

    Expanding access to office-based medication-assisted treatment with buprenorphine/naloxone for opioid dependence is a key part of the national strategy to address the opioid abuse epidemic (1). However, as buprenorphine/naloxone prescribing increased, emergency department (ED) visits and hospitalizations for unsupervised ingestions by young children began to increase, with buprenorphine/naloxone ingestions becoming the most common cause of hospitalization for medication ingestions by young children during 2010-2011 (2). Buprenorphine ingestions might be asymptomatic or can cause drowsiness, vomiting, or respiratory depression, which if untreated can result in death (3). Buprenorphine/naloxone was available only as tablets in multidose child-resistant bottles (Suboxone) until late 2010, when film strips packaged in unit-dose, child-resistant pouches were introduced. In 2013, tablets became available in unit-dose packaging (Zubsolv). Because unit-dose, child-resistant packaging encloses each dose until opened, it might limit unintended ingestions by young children compared with traditional child-resistant bottles that must be resecured after every use (4). This study compared ED visits for pediatric buprenorphine/naloxone ingestions before and after these product packaging/formulation changes.

  17. Voriconazole more likely than posaconazole increases plasma exposure to sublingual buprenorphine causing a risk of a clinically important interaction.

    Science.gov (United States)

    Fihlman, Mari; Hemmilä, Tuija; Hagelberg, Nora M; Kuusniemi, Kristiina; Backman, Janne T; Laitila, Jouko; Laine, Kari; Neuvonen, Pertti J; Olkkola, Klaus T; Saari, Teijo I

    2016-11-01

    This study aimed to determine possible effects of voriconazole and posaconazole on the pharmacokinetics and pharmacological effects of sublingual buprenorphine. We used a randomized, placebo-controlled crossover study design with 12 healthy male volunteers. Subjects were given a dose of 0.4 mg (0.6 mg during placebo phase) sublingual buprenorphine after a 5-day oral pretreatment with either (i) placebo, (ii) voriconazole 400 mg twice daily on the first day and 200 mg twice daily thereafter or (iii) posaconazole 400 mg twice daily. Plasma and urine concentrations of buprenorphine and its primary active metabolite norbuprenorphine were monitored over 18 h and pharmacological effects were measured. Compared to placebo, voriconazole increased the mean area under the plasma concentration-time curve (AUC 0-∞ ) of buprenorphine 1.80-fold (90 % confidence interval 1.45-2.24; P Voriconazole, unlike posaconazole, increased the urinary excretion of norbuprenorphine 1.58-fold (90 % confidence interval 1.18-2.12; P Voriconazole, and to a minor extent posaconazole, increase plasma exposure to sublingual buprenorphine, probably via inhibition of cytochrome P450 3 A and/or P-glycoprotein. Care should be exercised in the combined use of buprenorphine with triazole antimycotics, particularly with voriconazole, because their interaction can be of clinical importance.

  18. Comparison of subcutaneous and transdermal administration of buprenorphine for pre-emptive analgesia in dogs undergoing elective ovariohysterectomy.

    Science.gov (United States)

    Moll, Xavier; Fresno, Laura; García, Félix; Prandi, David; Andaluz, Anna

    2011-01-01

    The clinical efficacy of a 70 microg/h transdermal buprenorphine patch and of 20 microg/kg of buprenorphine administered subcutaneously (SC) for the relief of post-operative pain was determined in 24 healthy female dogs undergoing elective ovariohysterectomy (OHE). Dogs were randomly assigned to three groups: (1) a control group that received no analgesics, (2) a BSC group that received buprenorphine SC (20 microg/kg), and (3) a BP group that received buprenorphine by a 70 microg/h transdermal patch. Dogs were scored for signs of pain at 0, 2, 4, 6, 8, 10, 14, 20, 26, 32 and 38 h after extubation using the Numerical Rating Scale (NRS) and a modified University of Melbourne Pain Scale (UMPS). Mean NRS and UMPS scores for dogs in the BSC group (2.56 ± 0.23 and 3.05 ± 0.27, respectively) and the BP group (2.02 ± 0.24 and 2.67 ± 0.23, respectively) were significantly lower (Pbuprenorphine treatment groups were not significant. The results indicated that the analgesia produced by the 70 microg/h patch was similar to that induced by SC administration of 20 microg/kg of buprenorphine in dogs undergoing OHE, suggesting that the transdermal buprenorphine patch may be a useful alternative for pain management in dogs. 2009 Elsevier Ltd. All rights reserved.

  19. Assessment of drug-drug interactions between daclatasvir and methadone or buprenorphine-naloxone.

    Science.gov (United States)

    Garimella, T; Wang, R; Luo, W-L; Wastall, P; Kandoussi, H; DeMicco, M; Bruce, R D; Hwang, C; Bertz, R; Bifano, M

    2015-09-01

    Hepatitis C virus (HCV) infection is common among people who inject drugs, including those managed with maintenance opioids. Pharmacokinetic interactions between opioids and emerging oral HCV antivirals merit evaluation. Daclatasvir is a potent pangenotypic inhibitor of the HCV NS5A replication complex recently approved for HCV treatment in Europe and Japan in combination with other antivirals. The effect of steady-state daclatasvir (60 mg daily) on stable plasma exposure to oral opioids was assessed in non-HCV-infected subjects receiving methadone (40 to 120 mg; n = 14) or buprenorphine plus naloxone (8 to 24 mg plus 2 to 6 mg; n = 11). No relevant interaction was inferred if the 90% confidence interval (CI) of the geometric mean ratio (GMR) of opioid area under the plasma concentration-time curve over the dosing interval (AUCτ) or maximum concentration in plasma (C max) with versus without daclatasvir was within literature-derived ranges of 0.7 to 1.43 (R- and S-methadone) or 0.5 to 2.0 (buprenorphine and norbuprenorphine). Dose-normalized AUCτ for R-methadone (GMR, 1.08; 90% CI, 0.94 to 1.24), S-methadone (1.13; 0.99 to 1.30), and buprenorphine (GMR, 1.37; 90% CI, 1.24 to 1.52) were within the no-effect range. The norbuprenorphine AUCτ was slightly elevated in the primary analysis (GMR, 1.62; 90% CI, 1.30 to 2.02) but within the no-effect range in a supplementary analysis of all evaluable subjects. Dose-normalized C max for both methadone enantiomers, buprenorphine and norbuprenorphine, were within the no-effect range. Standardized assessments of opioid pharmacodynamics were unchanged throughout daclatasvir administration with methadone or buprenorphine. Daclatasvir pharmacokinetics were similar to historical data. Coadministration of daclatasvir and opioids was generally well tolerated. In conclusion, these data suggest that daclatasvir can be administered with buprenorphine or methadone without dose adjustments. Copyright © 2015, American Society for

  20. The introduction of buprenorphine-naloxone film in opioid substitution therapy in Australia: Uptake and issues arising from changing buprenorphine formulations.

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    Larance, Briony; Dietze, Paul; Ali, Robert; Lintzeris, Nicholas; White, Nancy; Jenkinson, Rebecca; Degenhardt, Louisa

    2015-11-01

    Buprenorphine-naloxone (BNX) film for opioid dependence treatment was introduced in Australia in 2011. A key difference in State policy approaches saw transfer from BNX tablets to BNX film mandated in South Australia (SA) with New South Wales (NSW) and Victoria (VIC) having less stringent policies. This study examined (i) how initiations and transfers were implemented, (ii) the profile and predictors of adverse effects as self-reported by BNX film clients, and (iii) dosing issues. Survey of 334 buprenorphine (BPN), BNX tablet and BNX film clients and semi-structured interviews with 39 key experts (KEs) in 2012. Comparisons are made between clients interviewed in SA versus NSW and VIC combined. Among the 180 current BNX film clients, 23% started treatment on BNX film, 18% requested a transfer to BNX film and 59% (n = 106) reported their clinic/prescriber recommended transfer to BNX film. Among clients who were offered but refused a transfer to BNX film (n = 66), the most common reason was 'I am happy with my current treatment and do not see a reason to change' (53%). Some opioid substitution therapy clients and KE viewed transfers as 'forced' (i.e. no choice of buprenorphine formulation). Multivariable regression showed residing in SA (vs. NSW/VIC) and a shorter length of current treatment episode were associated with more BNX film-attributed adverse effects but clinic/prescriber-recommended transfer was not. The introduction of BNX film in Australia varied across States. A perception of restricted choice in medication may have undermined initial acceptance in SA. © 2015 Australasian Professional Society on Alcohol and other Drugs.

  1. Role of buprenorphine in prolonging the duration of post-operative analgesia in percutaneous nephrolithotomy: Comparison between bupivacaine versus bupivacaine and buprenorphine combination

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    Jonnavithula Nirmala

    2015-01-01

    Full Text Available Introduction: Percutaneous nephrolithotomy (PCNL is the treatment of choice for large renal calculi. Pain around the nephrostomy tube is a clinical problem and we have previously reported alleviation of pain by peritubal block with bupivacaine, which lasted for 14 hours. The present study aimed to investigate the role of buprenorphine and bupivacaine combination in prolonging the duration of analgesia in peritubal block. Materials and Methods: A prospective, randomized controlled study was undertaken in 40 American Society of Anesthesiologists (ASA grade I and II patients who were scheduled for PCNL. Group I patients received 20 mL of 0.25% bupivacaine and group II patients received 20 mL of 0.25% bupivacaine with 100 μg of buprenorphine. Peritubal infiltration was given under fluoroscopic guidance along the nephrostomy tube from the renal capsule to the skin. Post-operative pain was assessed by Visual Analog Score (VAS, dynamic VAS (DVAS, sedation score, duration of analgesia and number of rescue analgesic demands. Rescue analgesia was inj tramadol 1 mg/kg IV if pain score exceeded 3. Results: Demographic data were comparable between the groups. Median duration of analgesia was 16 h in group I and 20 h in group II (P = 0.002. The maximum median VAS was 4 in group I and 2 in group II (P = 0.002. The median area under curve (AUC for VAS was 7 and 5 in groups I and II, respectively (P = 0.047. The median maximum DVAS in group I was 6 and 4 in group II. The median AUC for DVAS in 24 h was 16 in group I and 15 in group II (P = 0.017. Conclusions: Peritubal infiltration of 0.25% bupivacaine with 100 μg buprenorphine around a nephrostomy tube increased the duration of analgesia following PCNL without any side-effects.

  2. Efficacy and safety of a sublingual buprenorphine/naloxone rapidly dissolving tablet for the treatment of adults with opioid dependence: A randomized trial.

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    Webster, Lynn; Hjelmström, Peter; Sumner, Michael; Gunderson, Erik W

    2016-01-01

    This prospective, randomized, active-controlled, non-inferiority study evaluated the efficacy and safety of a sublingual buprenorphine/naloxone rapidly dissolving tablet (Zubsolv ® ; buprenorphine/naloxone rapidly dissolving tablet) versus generic buprenorphine for induction of opioid maintenance among dependent adults. The study, conducted at 13 sites from June 2013 to January 2014, included a 2-day blinded induction phase and a 27-day open-label stabilization/maintenance phase. During the blinded induction, patients received fixed doses of buprenorphine/naloxone rapidly dissolving tablets or generic buprenorphine. During open-label stabilization/early maintenance, all patients received buprenorphine/naloxone rapidly dissolving tablets. The primary efficacy assessment was treatment retention at day 3; buprenorphine/naloxone rapidly dissolving tablets were considered non-inferior to generic buprenorphine if the lower limit of the 95% confidence interval for the difference between the treatments was ≥-10% in patients retained on day 3. Secondary assessments included opioid withdrawal symptoms and cravings as measured using the Clinical Opiate Withdrawal Scale, the Subjective Opiate Withdrawal Scale, and the opioid cravings visual analogue scale. Safety was also assessed. A total of 313 patients were randomly assigned to induction with generic buprenorphine or buprenorphine/naloxone rapidly dissolving tablets. The mean age was 38.4 years, and the mean duration of opioid dependence was 12.4 years. For the primary efficacy assessment, 235 of 256 patients (91.8%) were retained at day 3 and continued to the maintenance phase. The lower limit of the 95% confidence interval was -13.7; thus, buprenorphine/naloxone rapidly dissolving tablets did not demonstrate non-inferiority to generic buprenorphine, and significantly more patients who received induction with generic buprenorphine (122/128 [95.3%]) were retained at day 3 compared with those who received induction with

  3. Nurse Practitioner Prescriptive Authority for Buprenorphine: From DATA 2000 to CARA 2016.

    Science.gov (United States)

    Fornili, Katherine S; Fogger, Susanne A

    The aim of this Policy Watch column is to provide an update on a much anticipated legislation, enacted in 2016, which enabled office-based opioid treatment (OBOT) with buprenorphine prescribing for the treatment of opioid addiction by nurse practitioners (as well as physician assistants). First, an overview of the Drug Addiction Treatment Act of 2000, which only permitted OBOT prescribing by physicians, will be described. It will be followed by a summary of the Recovery Enhancement for Addiction Treatment Act of 2015-2016. Finally, a review of the Comprehensive Addiction Recovery Act of 2016 will be provided, which includes information about important changes to OBOT regulations that enable NP prescribing of buprenorphine for the treatment of opioid addiction.

  4. Buprenorphine and methadone treatment for opioid dependence by income, ethnicity and race of neighborhoods in New York City

    Science.gov (United States)

    Hansen, Helena; Siegel, Carole; Wanderling, Joseph; DiRocco, Danae

    2016-01-01

    Background Geographic and demographic variation in buprenorphine and methadone treatment use in U.S. cities has not been assessed. Identifying variance in opioid maintenance is essential to improving treatment access and equity. Purpose To examine the differential uptake of buprenorphine treatment in comparison to methadone treatment between 2004 and 2013 in neighborhoods in New York City characterized by income, race and ethnicity. Methods Social area (SA) analysis of residential zip codes of methadone and buprenorphine patients in NYC, which aggregated zip codes into five social areas with similar percentages of residents below poverty, identifying as Black non-Hispanic and as Hispanic, to examine whether treatment rates differed significantly among social areas over time. For each rate, mixed model analyses of variance were run with fixed effects for social area, year and the interaction of social area by year. Results Buprenorphine treatment increased in all social areas over time with a significantly higher rate of increase in the social area with the highest income and the lowest percentage of Black, Hispanic, and low-income residents. Methadone treatment decreased slightly in all social areas until 2011 and then increased bringing rates back to 2004 levels. Treatment patterns varied by social area. Conclusions Buprenorphine treatment rates are increasing in all social areas, with slower uptake in moderate income mixed ethnicity areas. Methadone rates have remained stable over time. Targeted investments to promote public sector buprenorphine prescription may be necessary to reduce disparities in buprenorphine treatment and to realize its potential as a public health measure. PMID:27179822

  5. Beyond-use date determination of buprenorphine buccal solution using a stability-indicating high-performance liquid chromatographic assay.

    Science.gov (United States)

    Kirk, Loren Madden; Brown, Stacy D

    2015-12-01

    The objectives of this study included developing and validating a stability-indicating high-performance liquid chromatographic (HPLC) method with ultraviolet (UV) detection for the determination of buprenorphine in a buccal solution for veterinary use, and applying that method to determine the stability of a 3 mg/ml buprenorphine preparation in room temperature and refrigerated storage conditions. This preparation, intended for buccal administration in feline patients, plays an important role in pain management in cats. A stability-indicating HPLC method was developed and validated for system suitability, accuracy, repeatability, intermediate precision, specificity, linearity and robustness based on US Pharmacopeia (USP) General Chapter . The method was then applied to the study of potency changes over 90 days in a buccal buprenorphine solution stored at two temperatures. All HPLC-UV method data met acceptable criteria for the quantification of buprenorphine in a buccal solution formulation. The buprenorphine concentrations found in each stability sample remained within the 90-110% of label claim throughout the 90 days of study. All stability test bottles of the buprenorphine buccal solution retained their original appearance. For the room temperature bottles, some white particulate matter was noted in the threads of the container bottles starting at day 21. The pH of the preparations during the course of the study was in the range of 3.57-4.06 and 4.01-4.16 for the room temperature and refrigerated samples, respectively. Pharmacists have compounded a concentrated 3 mg/ml buccal solution to use easily in the home care or outpatient setting for treatment of feline pain. Prior to this investigation, pharmacists empirically assigned beyond-use dates to this formulation based on standards in USP General Chapter Pharmaceutical Compounding - Nonsterile Preparations. This study of a 3 mg/ml buprenorphine buccal solution indicates stability through 90 days. © ISFM and

  6. Sublingual Buprenorphine and Methadone Maintenance Treatment: A Three-Year Follow-Up of Quality of Life Assessment

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    Salvatore M. Giacomuzzi

    2005-01-01

    Full Text Available This study was conducted to compare long-term outcome effects on the quality of life (QOL of oral methadone with sublingual buprenorphine maintenance treatment. The QOL status of opioid-dependent patients was assessed using the German version (“Berlin Quality of Life Profile” of the Lancashire Quality of Life Profile. Physical symptoms were measured using the Opiate Withdrawal Scale (OWS. Urine tests were carried out randomly to detect additional consumption. In the first study period, 53 opioid-dependent subjects were enrolled and 25 could be reached after 3 years. The retention rate was 50% for methadone and 45% for buprenorphine (p = 0.786. Baseline values of the total sample (completers and noncompleters QOL and somatic complaints did not show significant differences between the two treatment groups. QOL characteristics at 6 months of treatment of the buprenorphine completer and noncompleter groups differed significantly regarding job (p = 0.013, family, and total score of physical symptoms (p = 0.002, in which the completer group showed the more favorable values. Concerning physical symptoms at 36 months, logistic regression revealed significantly less stomach cramps (p = 0.037 and fatigue and tiredness (p = 0.034 in buprenorphine compared to the methadone. Moreover, the buprenorphine-maintained group showed significantly less additional consumption of benzodiazepines (p = 0.015 compared with methadone participants. It is concluded that opioid addicts improved their QOL and health status when treated with methadone or buprenorphine. In summary, regarding QOL and health status, the present data indicate that buprenorphine is also a useful long-term alternative for maintenance treatment of opioid-dependent patients.

  7. Buprenorphine and methadone treatment for opioid dependence by income, ethnicity and race of neighborhoods in New York City.

    Science.gov (United States)

    Hansen, Helena; Siegel, Carole; Wanderling, Joseph; DiRocco, Danae

    2016-07-01

    Geographic and demographic variation in buprenorphine and methadone treatment use in U.S. cities has not been assessed. Identifying variance in opioid maintenance is essential to improving treatment access and equity. To examine the differential uptake of buprenorphine treatment in comparison to methadone treatment between 2004 and 2013 in neighborhoods in New York City characterized by income, race and ethnicity. Social area (SA) analysis of residential zip codes of methadone and buprenorphine patients in NYC, which aggregated zip codes into five social areas with similar percentages of residents below poverty, identifying as Black non-Hispanic and as Hispanic, to examine whether treatment rates differed significantly among social areas over time. For each rate, mixed model analyses of variance were run with fixed effects for social area, year and the interaction of social area by year. Buprenorphine treatment increased in all social areas over time with a significantly higher rate of increase in the social area with the highest income and the lowest percentage of Black, Hispanic, and low-income residents. Methadone treatment decreased slightly in all social areas until 2011 and then increased bringing rates back to 2004 levels. Treatment patterns varied by social area. Buprenorphine treatment rates are increasing in all social areas, with slower uptake in moderate income mixed ethnicity areas. Methadone rates have remained stable over time. Targeted investments to promote public sector buprenorphine prescription may be necessary to reduce disparities in buprenorphine treatment and to realize its potential as a public health measure. Copyright © 2016. Published by Elsevier Ireland Ltd.

  8. Comparative analgesic efficacy of buprenorphine or clonidine with bupivacaine in the caesarean section

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    Kiran Agarwal

    2010-01-01

    Full Text Available The need for early ambulation for caring of the neonate by mothers makes postoperative pain management after cesarean delivery unique. Favorable results have been observed with buprenorphine, clonidine and bupivacaine as epidural analgesics. This prospective, randomised triple blind control study was carried out among 112 lower segment caesarean segment (LSCS patients, divided into three groups, to assess the analgesic efficacy and side effects of epidural analgesia, with an intermittent top up of (i bupivacaine (0.125% and buprenorphine (0.075 mg (ii bupivacaine (0.125% and clonidine (37.5 microgram and (iii bupivacaine (0.125% alone, in LSCS cases. The demographic characteristics (age, weight and height of the three groups were comparable and the differences were not statistically significant. The mean duration of the analgesia was significantly longer in the group one patients receiving buprenorphine plus bupivacaine (690 ± 35 minutes and it was lowest in group three patients receiving bupivacaine (170 ± 31 minutes alone. The mean highest pain score (VAS scale was significantly lower (3.4 ± 0.6 in group one patients and it was highest in group three (6.7 ± 0.8 patients. Requirement of continuation of epidural analgesia after 15 hours of operation and requirement of diclonfenac injections as well as incidence of itching and pruritus was significantly lower in group one patients. Incidence of nausea and vomiting was the lowest in group one patients. Incidence of respiratory depression, sedation and hypotension were nil in all three group of patients. Epidural buprenorphine combined with bupivacaine produced significantly longer duration and better quality of analgesia than bupivacaine combined with clonidine or bupivacaine alone, and it was safe in LSCS patients, for post-operative analgesia.

  9. The safety of high-dose buprenorphine administered subcutaneously in cats.

    Science.gov (United States)

    Sramek, M K; Haas, M C; Coleman, G D; Atterson, P R; Hamlin, R L

    2015-10-01

    The safety of a proprietary formulation of buprenorphine hydrochloride administered subcutaneously (SC) to young cats was investigated in a blinded, randomized study. Four cohorts of eight cats aged approximately 4 months were administered saline, 0.24, 0.72 or 1.20 mg/kg/day buprenorphine SC for nine consecutive days, representing 0×, 1×, 3× and 5× of the intended dose. Cats were monitored daily for evidence of clinical reactions, food and water intake and adverse events (AEs). Physical examinations, clinical pathology, vital signs and electrocardiograms (ECGs) were evaluated at protocol-specified time points. Complete necropsy and histopathologic examinations were performed following humane euthanasia. Four buprenorphine-treated cats experienced AEs during the study, two unrelated and two related to study drug administration. The two cats with AEs considered related to drug administration had clinical signs of hyperactivity, difficulty in handling, disorientation, agitation and dilated pupils in one 0.24 mg/kg/day cat and one 0.72 mg/kg/day cat. All of these clinical signs were observed simultaneously. There were no drug-related effects on survival, injection response, injection site inspections, body weight, food or water consumption, bleeding time, urinalysis, respiration rate, heart rate, ECGs, blood pressures, body temperatures, macroscopic examinations or organ weights. Once daily buprenorphine s.c. injections at doses of 0.24, 0.72 and 1.20 mg/kg/day for 9 consecutive days were well tolerated in young domestic cats. © 2015 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  10. Comparison of the analgesic effects of robenacoxib, buprenorphine and their combination in cats after ovariohysterectomy.

    Science.gov (United States)

    Staffieri, F; Centonze, P; Gigante, G; De Pietro, L; Crovace, A

    2013-08-01

    The aim of this study was to compare the postoperative analgesic effects of robenacoxib and buprenorphine alone or in combination, in cats after ovariohysterectomy. Thirty healthy cats were randomly assigned to receive buprenorphine (0.02 mg/kg, n=10; GB), robenacoxib (2mg/kg, n=10; GR) or their combination at the same dosages (n=10; GBR) SC. After 30 min cats were sedated with an IM administration of medetomidine (0.02 mg/kg) and ketamine (5mg/kg). General anaesthesia was induced with propofol and after intubation was maintained with isoflurane. Before premedication and at 1, 2, 3, 4, 6, 8, 12 and 24h after extubation, pain and sedation were assessed using a simple descriptive pain scale, ranging from 0 (no pain/no sedation) to 4 (intense pain/ deep sedation). If the pain score was ≥ 3, rescue analgesia was provided using buprenorphine (0.02 mg/kg) administered IM. Pain score was higher in GB at 2, 3, 4, 6 and 8h compared to baseline and compared to GBR at the same study times. Moreover, the pain score was also higher in GB compared to GR at 2, 3, 4 and 6h. Pain score was similar at all study times between GR and GBR. Sedation at 1 and 2h was higher than baseline values in all groups. Cats in GB received rescue analgesia more often than cats assigned to GR or GBR. Robenacoxib was an effective analgesic drug in cats up to 24h after ovariohysterectomy. The addition of buprenorphine did not provide any additional analgesic effects compared to robenacoxib alone. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Psychoactive medications and disengagement from office based opioid treatment (obot) with buprenorphine.

    Science.gov (United States)

    Weinstein, Zoe M; Cheng, Debbie M; Quinn, Emily; Hui, David; Kim, Hyunjoong; Gryczynski, Gabriela; Samet, Jeffrey H

    2017-01-01

    The prevalence of psychoactive medications (PAMs) use in patients enrolled in Office Based Opioid Treatment (OBOT) and its association with engagement in this care is largely unknown. To describe the use of PAMs, including those medications with emerging evidence of misuse ("emerging PAMs" - gabapentin, clonidine and promethazine) among patients on buprenorphine, and its association with disengagement from OBOT. This is a retrospective cohort study of adults on buprenorphine from January 2002 to February 2014. The association between use of PAMs and 6-month disengagement from OBOT was examined using multivariable logistic regression models. A secondary analysis exploring time-to-disengagement was conducted using Cox regression models. At OBOT entry, 43% of patients (562/1308) were prescribed any PAM; including 17% (223/1308) on an emerging PAM. In separate adjusted analyses, neither the presence of any PAM (adjusted odds ratio [AOR] 1.07, 95% CI [0.78, 1.46]) nor an emerging PAM (AOR 1.28 [0.95, 1.74]) was significantly associated with 6-month disengagement. The results were similar for the Cox model (any PAM (adjusted hazard ratio [AHR] 1.16, 95% CI [1.00, 1.36]), emerging PAM (AHR 1.18 [0.98, 1.41])). Exploratory analyses suggested gabapentin (AHR 1.30 [1.05-1.62]) and clonidine (AHR 1.33 [1.01-1.73]) specifically, may be associated with an overall shorter time to disengagement. Psychoactive medication use is common among patients in buprenorphine treatment. No significant association was found between the presence of any psychoactive medications, including medications with emerging evidence of misuse, and 6-month disengagement from buprenorphine treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. New developments in managing opioid addiction: impact of a subdermal buprenorphine implant

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    Itzoe M

    2017-05-01

    Full Text Available MariaLisa Itzoe, Michael Guarnieri Department of Neurological Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA Abstract: Opioid addiction to prescription and illicit drugs is a serious and growing problem. In the US alone, >2.4 million people suffer from opioid use disorder. Government and pharmaceutical agencies have begun to address this crisis with recently released and revised task forces and medication-assisted therapies (MAT. For decades, oral or intravenous (IV MATs have helped patients in their recovery by administration of opioid agonists (methadone, buprenorphine, oxycodone, antagonists (naltrexone, naloxone, and combinations of the two (buprenorphine/naloxone. While shown to be successful, particularly when combined with psychological counseling, oral and IV forms of treatment come with constraints and challenges. Patients can become addicted to the agonists themselves, and there is increased risk for diversion, abuse, or missed dosages. Consequently, long-acting implants have begun to be developed as a potentially preferable method of agonist delivery. To date, the newest implant approved by the US Food and Drug Administration (May 2016 is Probuphine®, which delivers steady-state levels of buprenorphine over the course of 6 months. Numerous studies have demonstrated its efficacy and safety. Yet, implants come with their own risks such as surgical site irritation, possible movement, and protrusion of implant out of skin. This review introduces the opioid abuse epidemic, examines existing medications used for therapy, and highlights Probuphine as a new treatment option. Costs associated with MATs are also discussed. Keywords: addiction, opioids, medication-assisted therapy, long-acting implant, buprenorphine, Probuphine®

  13. The effect of buprenorphine and oxycodone on the intracholedochal passage pressure.

    Science.gov (United States)

    Tigerstedt, I; Turunen, M; Tammisto, T; Hästbacka, J

    1981-04-01

    The effect of i.v. buprenorphine (0.3 mg) and oxycodone (10mg) on intracholedochal passage pressure were studied in 20 patients who had undergone surgery of the common biliary tract, prior to the extraction of an indwelling T tube. Informed consent was obtained from all patients, each of who was given buprenorphine or oxycodone in random order. The intracholedochal passage pressure was measured from the T tube perfused with continuous saline infusion (55 ml/h). Both analgesics significantly (P less than 0.01) increased the intracholedochal passage pressure after 5 min, with an equal peak increase of about 1.5 kPa at about 7 min. The pressure decline was rapid and similar in both groups: 20 min after administration of the test drug only about 40% of the maximum elevation caused by either drug remained. Thereafter, a slower fall towards the baseline was recorded after both drugs during the remaining 45 min of the study period. The results indicate that buprenorphine can be used with the same indications and precautions as other narcotics for postoperative pain relief in patients who have undergone surgery of the biliary tract.

  14. Do methadone and buprenorphine have the same impact on psychopathological symptoms of heroin addicts?

    Science.gov (United States)

    2011-01-01

    Background The idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone) in a follow-up study lasting 12 months. Methods Drug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS) and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90), using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period. Results No statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology. Conclusions Heroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too. PMID:21569624

  15. Do methadone and buprenorphine have the same impact on psychopathological symptoms of heroin addicts?

    Directory of Open Access Journals (Sweden)

    Rugani Fabio

    2011-05-01

    Full Text Available Abstract Background The idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone in a follow-up study lasting 12 months. Methods Drug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90, using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period. Results No statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology. Conclusions Heroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too.

  16. Postoperative analgesic effects of dexketoprofen, buprenorphine and tramadol in dogs undergoing ovariohysterectomy.

    Science.gov (United States)

    Morgaz, J; Navarrete, R; Muñoz-Rascón, P; Domínguez, J M; Fernández-Sarmiento, J A; Gómez-Villamandos, R J; Granados, M M

    2013-08-01

    The objective of this study was to compare the postoperative analgesic effects of dexketoprofen, tramadol, and buprenorphine in dogs undergoing ovariohysterectomy. Seventy-five adult female dogs were randomly assigned to receive an intravenous injection (IV) of 1mg/kg of dexketoprofen (D), 0.02 mg/kg of buprenorphine (B) or 2mg/kg of tramadol (T). Pain assessment was performed during 48 h after ovariohysterectomy using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale (CMPS-SF). Rescue analgesia was required in 43%, 21%, and 5% of dogs in the B, T, and D groups, respectively, with significant differences between B and D (p=0.010) groups. The DIVAS and CMPS-SF values of the B group were significantly higher than those of the T and D groups. The most common undesirable effect was dysphoria in dexketoprofen group. Tramadol and dexketoprofen provide superior postoperative analgesia compared with buprenorphine in dogs undergoing ovariohysterectomy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Sedative and antinociceptive effects of dexmedetomidine and buprenorphine after oral transmucosal or intramuscular administration in cats.

    Science.gov (United States)

    Porters, Nathalie; Bosmans, Tim; Debille, Mariëlla; de Rooster, Hilde; Duchateau, Luc; Polis, Ingeborgh

    2014-01-01

    To compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats. Randomized, 'blinded' crossover study, with 1 month washout between treatments. Six healthy neutered female cats, weighing 5.3-7.5 kg. A combination of dexmedetomidine (40 μg kg(-1) ) and buprenorphine (20 μg kg(-1) ) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat's response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  18. Tobacco Addiction and Smoking Status in Heroin Addicts under Methadone vs. Buprenorphine Therapy

    Directory of Open Access Journals (Sweden)

    Rebecca Casari

    2012-03-01

    Full Text Available Aims of the present investigation were: (i to assess the prevalence of current smokers and relative smoking status among a large number of heroin addicts attending opioid-substitution therapy prevalence; (ii to evaluate the relationship between the type (methadone, buprenorphine and dosage of opioid substitution therapy and nicotine dependence. Three hundred and five (305 heroin addicts under opioid-substitution therapy were recruited at five Addiction Units. All participants completed a questionnaire assessing sociodemographic information, type and dose of opioid-substitution therapy, smoking history and status, Fagerström Test for Nicotine Dependence (FTND, and the Zung Self-Rating Depression scale (SDS. 298 subjects, out of 305 (97.2% were smokers, with an average of 20.5 cigarette/day and a median FTND of 6. Our data confirmed the high prevalence of smokers among heroin addicts, the highest described in the literature to date among heroin addicts under substitution therapies, without any significant difference between methadone vs. buprenorphine therapy groups. There was no correlation between dose of methadone or buprenorphine and average number of cigarettes/day. Patients in substance abuse treatment very frequently smoke cigarettes and often die of tobacco-related diseases. Substance abuse treatment programs too often ignore tobacco use. We hope that these findings will help to incorporate smoking cessation in substance abuse treatments.

  19. Treatment Outcomes of African American Buprenorphine Patients by Parole and Probation Status.

    Science.gov (United States)

    Mitchell, Shannon Gwin; Gryczynski, Jan; Kelly, Sharon M; O'Grady, Kevin E; Jaffe, Jerome H; Olsen, Yngvild K; Schwartz, Robert P

    2014-01-01

    This secondary analysis compared outcomes of African-American adults newly-admitted to buprenorphine treatment who were on parole and probation to patients who were not under criminal justice supervision. Buprenorphine patients (N=300) were randomly assigned to receive either Intensive Outpatient Treatment (IOP) or Standard Outpatient Treatment (OP) treatment and were assessed at baseline, 3- and 6-months. There were no differences between groups in treatment retention. Among probationers/parolees, IOP was associated with lower 3-month treatment retention compared to OP, but among participants not on probation/parole the relationship was reversed (p=.004). Both conditions showed significant declines in heroin and cocaine use, illegal activity, and in meeting DSM-IV criteria for opioid and cocaine dependence. Probationers/parolees reported lower frequency of illegal activities at 3-months compared to non-probationers/parolees (p=.007). Buprenorphine treatment should be made more widely available to individuals on parole/probation as they respond as well to treatment as patients not supervised by the criminal justice system.

  20. Effects of buprenorphine, meloxicam, and flunixin meglumine as postoperative analgesia in mice.

    Science.gov (United States)

    Tubbs, Jacquelyn T; Kissling, Grace E; Travlos, Greg S; Goulding, David R; Clark, James A; King-Herbert, Angela P; Blankenship-Paris, Terry L

    2011-03-01

    C57BL/6NCrl male mice (n = 60; age, 6 to 7 wk) underwent partial hepatectomy or no surgery and were given 1 of 3 analgesics pre- and postoperatively. Food and water consumption, body weight, running wheel activity, locomotor activity, and serum corticosterone concentrations were measured before and after surgery. Mice that were surgically manipulated weighed significantly less on days 1 through 3 after surgery than did mice not manipulated surgically. On the day of surgery, the surgery groups consumed significantly less feed (-1.5±0.35 g) than did nonsurgery groups. There were no differences in water consumption on any day between surgery and nonsurgery groups or among the 3 analgesic groups. For running wheel activity, significant decreases in the surgery groups were seen at day 1 after surgery compared with baseline. Surgery groups that received buprenorphine and meloxicam returned to baseline activity levels on day 2 after surgery. Open-field testing revealed no significant differences in locomotor activity in any groups; however, posttreatment locomotor activity in the buprenorphine nonsurgery group was increased compared with baseline, and posttreatment locomotor activity in the flunixin meglumine surgery group was decreased compared with baseline. Serum corticosterone concentrations were within normal limits regardless of treatment in all groups. Comparison of the overall results indicated that meloxicam and buprenorphine, at the dose given, appear to be suitable postoperative analgesics for partial hepatectomy in mice. Flunixin meglumine at the given dosage (2.5 mg/kg) may not provide adequate analgesia for partial hepatectomy.

  1. Determination of buprenorphine, fentanyl and LSD in whole blood by UPLC-MS-MS.

    Science.gov (United States)

    Berg, Thomas; Jørgenrud, Benedicte; Strand, Dag Helge

    2013-04-01

    A sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method has been developed and validated for the quantification of buprenorphine, fentanyl and lysergic acid diethylamide (LSD) in whole blood. Sample preparation was performed by liquid-liquid extraction (LLE) with methyl tert-butyl ether. UPLC-MS-MS analysis was performed with a mobile phase consisting of ammonium formate (pH 10.2) and methanol. Positive electrospray ionization MS-MS detection was performed with two multiple reaction monitoring transitions for each of the analytes and the deuterium labeled internal standards. Limit of detection values of buprenorphine, fentanyl and LSD were 0.28, 0.044 and 0.0097 ng/mL and limit of quantification values were 0.94, 0.14 and 0.036 ng/mL, respectively. Most phospholipids were removed during LLE. No or only minor matrix effects were observed. The method has been routinely used at the Norwegian Institute of Public Health since September 2011 for qualitative and quantitative detections of buprenorphine, fentanyl and/or LSD in more than 400 whole blood samples with two replicates per sample.

  2. Home- versus office-based buprenorphine inductions for opioid-dependent patients.

    Science.gov (United States)

    Sohler, Nancy L; Li, Xuan; Kunins, Hillary V; Sacajiu, Galit; Giovanniello, Angela; Whitley, Susan; Cunningham, Chinazo O

    2010-03-01

    Recent legislation permits the treatment of opioid-dependent patients with buprenorphine in the primary care setting, opening doors for the development of new treatment models for opioid dependence. We modified national buprenorphine treatment guidelines to emphasize patient self-management by giving patients the opportunity to choose to have buprenorphine inductions at home or the physician's office. We examined whether patients who had home-based inductions achieved greater 30-day retention than patients who had traditional office-based inductions in a study of 115 opioid-dependent patients treated in an inner-city health center. Retention was similar in both groups: 50 (78.1%) in office-based group versus 40 (78.4%) in home-based group, p = .97. Several patient characteristics were associated with choosing office- versus home-based inductions, which likely influenced these results. We conclude that opioid dependence can be successfully managed in the primary care setting. Approaches that encourage patient involvement in treatment for opioid dependence can be beneficial. Copyright 2010 Elsevier Inc. All rights reserved.

  3. Pharmacokinetics of buprenorphine following intravenous and buccal administration in cats, and effects on thermal threshold.

    Science.gov (United States)

    Hedges, A R; Pypendop, B H; Shilo-Benjamini, Y; Stanley, S D; Ilkiw, J E

    2014-06-01

    This study reports the pharmacokinetics of buprenorphine, following i.v. and buccal administration, and the relationship between buprenorphine concentration and its effect on thermal threshold. Buprenorphine (20 μg/kg) was administered intravenously or buccally to six cats. Thermal threshold was determined, and arterial blood sampled prior to, and at various times up to 24 h following drug administration. Plasma buprenorphine concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to the time-concentration data. Pharmacokinetic/pharmacodynamic models were fitted to the concentration-thermal threshold data. Thermal threshold was significantly higher than baseline 44 min after buccal administration, and 7, 24, and 104 min after i.v. administration. A two- and three-compartment model best fitted the data following buccal and i.v. administration, respectively. Following i.v. administration, mean ± SD volume of distribution at steady-state (L/kg), clearance (mL·min/kg), and terminal half-life (h) were 11.6 ± 8.5, 23.8 ± 3.5, and 9.8 ± 3.5. Following buccal administration, absorption half-life was 23.7 ± 9.1 min, and terminal half-life was 8.9 ± 4.9 h. An effect-compartment model with a simple effect maximum model best predicted the time-course of the effect of buprenorphine on thermal threshold. Median (range) ke0 and EC50 were 0.003 (0.002-0.018)/min and 0.599 (0.073-1.628) ng/mL (i.v.), and 0.017 (0.002-0.023)/min and 0.429 (0.144-0.556) ng/mL (buccal). © 2013 John Wiley & Sons Ltd.

  4. Arrhythmia associated with buprenorphine and methadone reported to the Food and Drug Administration.

    Science.gov (United States)

    Kao, David P; Haigney, Mark C P; Mehler, Philip S; Krantz, Mori J

    2015-09-01

    To assess the relative frequency of reporting of adverse events involving ventricular arrhythmia, cardiac arrest, corrected QT interval (QTc) prolongation or torsade de pointes to the US Food and Drug Administration (FDA) between buprenorphine and methadone. Retrospective pharmacoepidemiological study. Adverse drug events reported spontaneously to the FDA between 1969 and June 2011 originating in 196 countries (71% events from the United States). Adverse event cases mentioning methadone (n = 14 915) or buprenorphine (n = 7283) were evaluated against all other adverse event cases (n = 4 796 017). The primary outcome was the composite of ventricular arrhythmia or cardiac arrest. The secondary outcome was the composite of QTc prolongation or torsade de pointes. The proportional reporting ratio (PRR) was used to identify disproportionate reporting defined as a PRR > 2, χ(2) error > 4, with ≥ 3 cases. There were 132 (1.8%) ventricular arrhythmia/cardiac arrest and 19 (0.3%) QTc prolongation/torsade de pointes cases associated with buprenorphine compared with 1729 (11.6%) ventricular arrhythmia/cardiac arrest and 390 (2.6%) QTc prolongation/torsade de pointes cases involving methadone. PRRs associated with buprenorphine were not significant for ventricular arrhythmia/cardiac arrest (1.10, 95%, confidence interval (0.93-1.31, χ(2)  = 1.2) or QTc prolongation/torsade de pointes (1.03, 95% CI = 0.66-1.62, χ(2)  = 0.01), but were for methadone (7.20, 95% CI = 6.88-7.52, χ(2)  = 8027; 10.7, 95% CI = 9.66-11.8, χ(2)  = 1538, respectively). In spontaneously reported adverse events, methadone is associated with disproportionate reporting of cardiac arrhythmias, whereas buprenorphine is not. Although these findings probably reflect clinically relevant differences, a causal connection cannot be presumed and disproportionality analysis cannot quantify absolute risk per treatment episode. Population-based studies to

  5. Long-term retention in Office Based Opioid Treatment with buprenorphine.

    Science.gov (United States)

    Weinstein, Zoe M; Kim, Hyunjoong W; Cheng, Debbie M; Quinn, Emily; Hui, David; Labelle, Colleen T; Drainoni, Mari-Lynn; Bachman, Sara S; Samet, Jeffrey H

    2017-03-01

    Guidelines recommend long-term treatment for opioid use disorder with buprenorphine; however, little is known about patients in long-term treatment. The aim of this study is to examine the prevalence and patient characteristics of long-term treatment retention (≥1year) in an Office Based Opioid Treatment (OBOT) program with buprenorphine. This is a retrospective cohort study of adults on buprenorphine from January 2002 to February 2014 in a large urban safety-net primary care OBOT program. The primary outcome was retention in OBOT for at least one continuous year. Potential predictors included age, race, psychiatric diagnoses, hepatitis C, employment, prior buprenorphine, ever heroin use, current cocaine, benzodiazepine and alcohol use on enrollment. Factors associated with ≥1year OBOT retention were identified using generalized estimating equation logistic regression models. Patients who re-enrolled in the program contributed repeated observations. There were 1605 OBOT treatment periods among 1237 patients in this study. Almost half, 45% (717/1605), of all treatment periods were ≥1year and a majority, 53.7% (664/1237), of patients had at least one ≥1year period. In adjusted analyses, female gender (Adjusted Odds Ratio [AOR] 1.55, 95% CI [1.20, 2.00]) psychiatric diagnosis (AOR 1.75 [1.35, 2.27]) and age (AOR 1.19 per 10year increase [1.05, 1.34]) were associated with greater odds of ≥1year retention. Unemployment (AOR 0.72 [0.56, 0.92]), Hepatitis C (AOR 0.59 [0.45, 0.76]), black race/ethnicity (AOR 0.53 [0.36, 0.78]) and Hispanic race/ethnicity (AOR 0.66 [0.48, 0.92]) were associated with lower odds of ≥1year retention. Over half of patients who presented to Office Based Opioid Treatment with buprenorphine were ultimately successfully retained for ≥1year. However, significant disparities in one-year treatment retention were observed, including poorer retention for patients who were younger, black, Hispanic, unemployed, or with hepatitis C. Copyright

  6. "Sub is a weird drug:" A web-based study of lay attitudes about use of buprenorphine to self-treat opioid withdrawal symptoms.

    Science.gov (United States)

    Daniulaityte, Raminta; Carlson, Robert; Brigham, Gregory; Cameron, Delroy; Sheth, Amit

    2015-08-01

    Illicit use of buprenorphine has increased in the U.S., but our understanding of its use remains limited. This study aims to explore Web-forum discussions about the use of buprenorphine to self-treat opioid withdrawal symptoms. PREDOSE, a novel Semantic Web platform, was used to extract relevant posts from a Web-forum that allows free discussions on illicit drugs. First, we extract information about the total number of buprenorphine-related posts per year between 2005 and 2013. Second, PREDOSE was used to identify all posts that potentially contained discussions about buprenorphine and opioid withdrawal. A total number of 1,217 posts that contained these terms were extracted and entered into NVivo data base. A random sample of 404 (33%) posts was selected and content analyzed. Buprenorphine-related posts increased over time, peaking in 2011. The posts were about equally divided between those that expressed positive and negative views about the effectiveness of buprenorphine in relieving withdrawal symptoms. Web-forum participants emphasized that buprenorphine's effectiveness may become compromised because of the "size of a person habit," and/or when users repeatedly switch back and forth between buprenorphine and other illicit opioids. Most posts reported use of significantly lower amounts of buprenorphine (≤2 mg) than doses used in standard treatment. Concomitant use of other psychoactive substances was also commonly reported, which may present significant health risks. Our findings highlight the usefulness of Web-based data in drug abuse research and add new information about lay beliefs about buprenorphine that may help inform prevention and policy measures. © American Academy of Addiction Psychiatry.

  7. Inhibition of CYP2D6-mediated tramadol O-demethylation in methadone but not buprenorphine maintenance patients

    Science.gov (United States)

    Coller, Janet K; Michalakas, Jennifer R; James, Heather M; Farquharson, Aaron L; Colvill, Joel; White, Jason M; Somogyi, Andrew A

    2012-01-01

    AIMS To compare the O- (CYP2D6 mediated) and N- (CYP3A4 mediated) demethylation metabolism of tramadol between methadone and buprenorphine maintained CYP2D6 extensive metabolizer subjects. METHODS Nine methadone and seven buprenorphine maintained subjects received a single 100 mg dose of tramadol hydrochloride. Blood was collected at 4 h and assayed for tramadol, methadone, buprenorphine and norbuprenorphine (where appropriate) and all urine over 4 h was assayed for tramadol and its M1 and M2 metabolites. RESULTS The urinary metabolic ratio [median (range)] for O-demethylation (M1) was significantly lower (P= 0.0002, probability score 1.0) in the subjects taking methadone [0.071 (0.012–0.103)] compared with those taking buprenorphine [0.192 (0.108–0.392)], but there was no significant difference (P= 0.21, probability score 0.69) in N-demethylation (M2). The percentage of dose [median (range)] recovered as M1 was significantly lower in subjects taking methadone compared with buprenorphine (0.069 (0.044–0.093) and 0.126 (0.069–0.187), respectively, P= 0.04, probability score 0.19), M2 was significantly higher in subjects taking methadone compared with buprenorphine (0.048 (0.033–0.085) and 0.033 (0.014–0.049), respectively, P= 0.04, probability score 0.81). Tramadol was similar (0.901 (0.635–1.30) and 0.685 (0.347–1.04), respectively, P= 0.35, probability score 0.65). CONCLUSIONS Methadone inhibited the CYP2D6-mediated metabolism of tramadol to M1. Hence, as the degree of opioid analgesia is largely dependent on M1 formation, methadone maintenance patients may not receive adequate analgesia from oral tramadol. PMID:22369095

  8. Treatment readiness, attitudes toward, and experiences with methadone and buprenorphine maintenance therapy among people who inject drugs in Malaysia.

    Science.gov (United States)

    Vijay, Aishwarya; Bazazi, Alexander R; Yee, Ilias; Kamarulzaman, Adeeba; Altice, Frederick L

    2015-07-01

    Little is known about attitudes toward and experiences with opioid maintenance therapy (OMT) among people who inject drugs in Malaysia, a country where people who inject drugs comprise 1.3% of the adult population. In 2010, 460 people who inject drugs in Greater Kuala Lumpur, Malaysia were surveyed to evaluate attitudes toward and experiences with OMT and treatment readiness. Attitudes towards OMT with both methadone and buprenorphine were assessed using an opinions scale. Multivariable linear regression was used to assess correlates of treatment readiness, measured with the 19-item Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). All 460 participants used opioids and nearly all (99.1%) met criteria for opioid dependence. Few had had previous experience with methadone (9.3%) or buprenorphine (12.6%) maintenance therapy, yet many had used methadone (55.2%) or buprenorphine (51.7%) outside of treatment settings. Fifteen percent had injected buprenorphine in the past month, and of the few that were currently receiving buprenorphine maintenance therapy, almost all were injecting it. The majority of subjects exhibited a moderate level of treatment readiness and a preference for methadone over buprenorphine. Those with low treatment readiness scores were more likely to have previous experience with compulsory drug detention centers (pstress symptom severity (p<0.001), and sharing of needles or syringes (p<0.05) were associated with higher treatment readiness scores. There are suboptimal levels of OMT experience among people who inject drugs that may be improved by addressing factors that influence patient attitudes. Those individuals with moderate treatment readiness may be targeted by brief motivational and cognitive interventions in primary care, prisons or OMT clinics aimed at improving entry into and retention in treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Characteristics of veterans receiving buprenorphine vs. methadone for opioid use disorder nationally in the Veterans Health Administration.

    Science.gov (United States)

    Manhapra, Ajay; Quinones, Lantie; Rosenheck, Robert

    2016-03-01

    The advent of buprenorphine as an alternative to methadone has dramatically shifted the landscape of opioid agonist therapy (OAT) for opioid use disorder (OUD). However, there is limited US national level data describing thedifferences between patients who are prescribed these two OAT options. From veterans with OUD diagnosis who used Veterans Health Administration services in 2012, we identified 3 mutually exclusive groups: those who received (1) buprenorphine only (n=5,670); (2) methadone only (n=6,252); or (3) both buprenorphine and methadone in the same year (n=2513). We calculated the bi-varate effect size differences (risk ratios and Cohen's d) forcharacteristics that differentiated these groups. Logistic regression analysis was then used to identify factors independently differentiating the groups. Ten year increment in age (OR 0.67; 95% CI 0.64-0.70), urban residence (OR 0.26; 95% CI 0.25-0.33), and black race (OR 0.39; 95% CI 0.35-0.43) were strongly and negatively associated with odds of receiving buprenorphine compared to methadone, while medical and psychiatric comorbidities or receipt of other psychiatric medications did not demonstrate substantial differences between groups. Differences between veterans receiving buprenorphine or methadone based OAT seems to be largely shaped by demographic characteristics rather than medical or psychiatric or service use characteristics. A clearer understanding of the reasons for racial differences could be helpful in assuring that black OUD patients are not denied the opportunity to receive buprenorphine if that is their preference. Published by Elsevier Ireland Ltd.

  10. Tramadol and the risk of fracture in an elderly female population: a cost utility assessment with comparison to transdermal buprenorphine.

    Science.gov (United States)

    Hirst, Alexander; Knight, Chris; Hirst, Matt; Dunlop, Will; Akehurst, Ron

    2016-03-01

    Opioid treatment for chronic pain is a known risk factor for falls and/or fractures in elderly patients. The latter cause a significant cost to the National Health Service and the Personal Social Services in the UK. Tramadol has a higher risk of fractures than some other opioid analgesics used to treat moderate-to-severe pain and, in the model described here, we investigate the cost effectiveness of transdermal buprenorphine treatment compared with tramadol in a high-risk population. A model was developed to assess the cost effectiveness of tramadol compared with transdermal buprenorphine over a 1-year time horizon and a patient population of high-risk patients (female patients age 75 or older). To estimate the total cost and quality-adjusted life years (QALYs) of treatment, published odds ratios are used in combination with the published incidence rates of four types of fracture: hip, wrist, humerus and other. The model shows tramadol to be associated with 1,058 more fractures per 100,000 patients per year compared with transdermal buprenorphine, resulting in transdermal buprenorphine being cost-effective with an incremental cost-effectiveness ratio of less than £7,000 compared with tramadol. Sensitivity analysis found this result to be robust. In the UK data, there is uncertainty regarding the transdermal buprenorphine odds ratios for fractures. Odds ratios published in Danish and Swedish studies show similar point estimates but are associated with less uncertainty. Transdermal buprenorphine is cost-effective compared to tramadol at a willingness-to-pay threshold of £20,000 per QALY.

  11. Long-Acting Injectable Naltrexone Induction: A Randomized Trial of Outpatient Opioid Detoxification With Naltrexone Versus Buprenorphine.

    Science.gov (United States)

    Sullivan, Maria; Bisaga, Adam; Pavlicova, Martina; Choi, C Jean; Mishlen, Kaitlyn; Carpenter, Kenneth M; Levin, Frances R; Dakwar, Elias; Mariani, John J; Nunes, Edward V

    2017-05-01

    At present there is no established optimal approach for transitioning opioid-dependent adults to extended-release injection naltrexone (XR-naltrexone) while preventing relapse. The authors conducted a trial examining the efficacy of two methods of outpatient opioid detoxification for induction to XR-naltrexone. Participants were 150 opioid-dependent adults randomly assigned 2:1 to one of two outpatient detoxification regimens, naltrexone-assisted detoxification or buprenorphine-assisted detoxification, followed by an injection of XR-naltrexone. Naltrexone-assisted detoxification lasted 7 days and included a single day of buprenorphine followed by ascending doses of oral naltrexone along with clonidine and other adjunctive medications. Buprenorphine-assisted detoxification included a 7-day buprenorphine taper followed by a week-long delay before administration of XR-naltrexone, consistent with official prescribing information for XR-naltrexone. Participants from both groups received behavioral therapy focused on medication adherence and a second dose of XR-naltrexone. Compared with participants in the buprenorphine-assisted detoxification condition, participants assigned to naltrexone-assisted detoxification were significantly more likely to be successfully inducted to XR-naltrexone (56.1% compared with 32.7%) and to receive the second injection at week 5 (50.0% compared with 26.9%). Both models adjusted for primary type of opioid use, route of opioid administration, and morphine equivalents at baseline. These results demonstrate the safety, efficacy, and tolerability of low-dose naltrexone, in conjunction with single-day buprenorphine dosing and adjunctive nonopioid medications, for initiating adults with opioid dependence to XR-naltrexone. This strategy offers a promising alternative to the high rates of attrition and relapse currently observed with agonist tapers in both inpatient and outpatient settings.

  12. Self-reported side effects in buprenorphine and methadone patients receiving antiretroviral therapy: results from the MANIF 2000 cohort study.

    Science.gov (United States)

    Carrieri, M Patrizia; Roux, Perrine; Cohen, Julien; Ravaux, Isabelle; Dellamonica, Pierre; Protopopescu, Camelia; Spire, Bruno; Rosenblum, Andrew

    2010-12-01

    The aim of the study was to investigate the relationship between methadone and buprenorphine treatment and self-reported symptoms in HIV-infected opioid dependent individuals receiving antiretroviral therapy (ART). Longitudinal study. The French MANIF2000 cohort was used to compare self-reported symptoms in buprenorphine and methadone patients also receiving ART. We selected individuals receiving ART and OAT (342 visits among 106 patients). Symptoms were self-reported using a list of 14 symptoms (e.g. nausea, fatigue, fever) perceived during the previous 4 weeks, including three painful symptoms (abdominal or muscular pain, headaches). A two-step Heckman approach enabled us to account for the non-random assignment of OAT: a probit model identified predictors of starting either buprenorphine or methadone. A Poisson regression based on generalized estimating equations (GEE) was then used to identify predictors of the number of symptoms while adjusting for the non-random assignment of OAT. The median (interquartile range) number of symptoms was 4 (1-6) and 2 (1-6) among buprenorphine and methadone patients, respectively. After adjustment for non-random assignment of OAT type, depressive and opioid withdrawal symptoms, anxiolytics consumption and daily cannabis use, methadone patients were more likely to report a lower number of symptoms than those receiving buprenorphine. Methadone patients on ART report fewer symptoms than buprenorphine patients on ART under current treatment conditions in France. Further experimental research is still needed to identify an OAT-ART strategy which would minimize the burden of self-reported symptoms and potential interactions, while assuring sustainability and response to both treatments. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

  13. Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study.

    Science.gov (United States)

    Ling, Walter; Hillhouse, Maureen P; Saxon, Andrew J; Mooney, Larissa J; Thomas, Christie M; Ang, Alfonso; Matthews, Abigail G; Hasson, Albert; Annon, Jeffrey; Sparenborg, Steve; Liu, David S; McCormack, Jennifer; Church, Sarah; Swafford, William; Drexler, Karen; Schuman, Carolyn; Ross, Stephen; Wiest, Katharina; Korthuis, P Todd; Lawson, William; Brigham, Gregory S; Knox, Patricia C; Dawes, Michael; Rotrosen, John

    2016-08-01

    To examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone(®) ) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol(®) ) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. This multi-centered, double-blind, placebo-controlled study, conducted under the auspices of the National Drug Abuse Treatment Clinical Trials Network, randomly assigned 302 participants at sites in California, Oregon, Washington, Colorado, Texas, Georgia, Ohio, New York and Washington DC, USA to one of three conditions provided with XR-NTX: 4 mg/day BUP (BUP4, n = 100), 16 mg/day BUP (BUP16, n = 100, or no buprenorphine (placebo; PLB, n = 102). Participants received pharmacotherapy for 8 weeks, with three clinic visits per week. Cognitive behavioral therapy was provided weekly. Follow-up assessments occurred at 1 and 3 months post-intervention. The planned primary outcome was urine drug screen (UDS)-corrected, self-reported cocaine use during the last 4 weeks of treatment. Planned secondary analyses assessed cocaine use by UDS, medication adherence, retention and adverse events. No group differences were found between groups for the primary outcome (BUP4 versus PLB, P = 0.262; BUP16 versus PLB, P = 0.185). Longitudinal analysis of UDS data during the evaluation period using generalized linear mixed equations found a statistically significant difference between BUP16 and PLB [P = 0.022, odds ratio (OR) = 1.71] but not for BUP4 (P = 0.105, OR = 1.05). No secondary outcome differences across groups were found for adherence, retention or adverse events. Buprenorphine + naloxone, used in combination with naltrexone, may be associated with reductions in cocaine use among people who meet DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. © 2016 Society for the Study of

  14. Messages about methadone and buprenorphine in reality television: a content analysis of celebrity rehab with Dr. Drew.

    Science.gov (United States)

    Roose, Robert; Fuentes, Liza; Cheema, Mandeep

    2012-08-01

    Medication-assisted treatment for opioid dependence is safe and effective, yet negative perceptions about methadone and buprenorphine may discourage patients from entering treatment. One source of information that may influence viewers' perceptions is television. We performed a content analysis of a popular reality television program on addiction treatment. Although many patients had histories of opioid use, there were no positive messages about methadone or buprenorphine. The two main messages were that they (1) are primarily drugs of abuse, and (2) not acceptable treatment options. These messages reinforce negative stereotypes and may perpetuate stigma. There were multiple missed opportunities to provide evidence-based information.

  15. Determination of an optimal dose of medetomidine-ketamine-buprenorphine for anaesthesia in the Cape ground squirrel (Xerus inauris)

    OpenAIRE

    K. E. Joubert; T. Serfontein; M. Scantlebury; M B Manjerovic; P. W. Bateman; M B Manjerovic; P. W. Bateman; N. C. Bennett; J. M. Waterman

    2011-01-01

    The optimal dose of medetomidine-ketamine-buprenorphine was determined in 25 Cape ground squirrels (Xerus inauris) undergoing surgical implantation of a temperature logger into the abdominal cavity. At the end of anaesthesia, the squirrels were given atipamezole intramuscularly to reverse the effects of medetomidine. The mean dose of medetomidine was 67.6±9.2 μg/kg, ketamine 13.6±1.9 mg/kg and buprenorphine 0.5±0.06 μg/kg. Induction time was 3.1 ± 1.4 min. This produced surgical anaesthesia f...

  16. Preliminary investigation comparing a detomidine continuous rate infusion combined with either morphine or buprenorphine for standing sedation in horses

    OpenAIRE

    Potter, Joanna J.; Macfarlane, Paul D.; Love, Emma J.; Tremaine, Henry; Taylor, Polly M; Murrell, Joanna C.

    2016-01-01

    Objective: To compare sedative and analgesic properties of buprenorphine or morphine for standing procedures combined with a detomidine continuous rate infusion (CRI). Study design: Blinded, prospective, randomized clinical pilot study. Animals: Ten horses presented for dental or sinus procedures. Methods: Horses received 0.02 mg kg-1 acepromazine intravenously (IV), followed 30 minutes later by detomidine 10 μg kg-1 IV. Five minutes later, buprenorphine 0.01 mg kg-1 (n = 6) or morphine 0.1 m...

  17. Preliminary investigation comparing a detomidine continuous rate infusion combined with either morphine or buprenorphine for standing sedation in horses.

    Science.gov (United States)

    Potter, Joanna J; MacFarlane, Paul D; Love, Emma J; Tremaine, Henry; Taylor, Polly M; Murrell, Joanna C

    2016-03-01

    To compare sedative and analgesic properties of buprenorphine or morphine for standing procedures combined with a detomidine continuous rate infusion (CRI). Blinded, prospective, randomized clinical pilot study. Ten horses presented for dental or sinus procedures. Horses received 0.02 mg kg(-1) acepromazine intravenously (IV), followed 30 minutes later by detomidine 10 μg kg(-1) IV. Five minutes later, buprenorphine 0.01 mg kg(-1) (n = 6) or morphine 0.1 mg kg(-1) (n = 4) was administered IV. Detomidine was administered by CRI (0.2 μg kg(-1) minute(-1)) and adjusted to maintain appropriate sedation. Heart rate, respiratory frequency, gastrointestinal motility and rectal temperature were measured; pain, ataxia and sedation were scored. Sedation, pain scores and ataxia scores were analysed using a mixed linear model. Detomidine dose and procedure success scores were compared using Wilcoxon's rank sum test. Complications between groups were analysed using Fisher's exact test. Two horses had incomplete data. Weights and ages were not different between groups (p = 0.15 and p = 0.42, respectively). The dose rate for detomidine was not different between groups (0.33 ± 0.02 μg kg(-1) minute(-1) in the buprenorphine group and 0.33 ± 0.05 μg kg(-1) minute(-1), in the morphine group p = 0.89). Intraoperative visual analogue scale scores were greater after buprenorphine than morphine (mean ± SD, buprenorphine 48 ± 4, morphine 40 ± 5, p = 0.0497). Procedure duration was not different between groups (buprenorphine 142 ± 33, morphine 140 ± 12 minutes). All horses treated with buprenorphine experienced complications compared with none in the morphine group (p = 0.0286). At the doses used, buprenorphine produced greater sedation but more post-operative complications than morphine. However, Type I or Type II errors cannot be excluded and larger studies are required to confirm these findings. © 2015 Association of Veterinary Anaesthetists and the American College of

  18. A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings

    Directory of Open Access Journals (Sweden)

    Keele E. Wurst

    2016-01-01

    Full Text Available Background Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy. Objective The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden. Methods Pregnant women and their corresponding births during 2005–2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher's exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population. Results A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine ( N = 176 or methadone ( N = 52, no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby's father. Conclusions An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine

  19. Epidural analgesia with morphine or buprenorphine in ponies with lipopolysaccharide (LPS)-induced carpal synovitis.

    Science.gov (United States)

    Freitas, Gabrielle C; Carregaro, Adriano B; Gehrcke, Martielo I; De La Côrte, Flávio D; Lara, Valéria M; Pozzobon, Ricardo; Brass, Karin E

    2011-04-01

    This study evaluated the analgesia effects of the epidural administration of 0.1 mg/kg bodyweight (BW) of morphine or 5 μg/kg BW of buprenorphine in ponies with radiocarpal joint synovitis. Six ponies were submitted to 3 epidural treatments: the control group (C) received 0.15 mL/kg BW of a 0.9% sodium chloride (NaCl) solution; group M was administered 0.1 mg/kg BW of morphine; and group B was administered 5 μg/kg BW of buprenorphine, both diluted in 0.9% NaCl to a total volume of 0.15 mL/kg BW administered epidurally at 10 s/mL. The synovitis model was induced by injecting 0.5 ng of lipopolysaccharide (LPS) in the left or right radiocarpal joint. An epidural catheter was later introduced in the lumbosacral space and advanced up to the thoracolumbar level. The treatment started 6 h after synovitis induction. Lameness, maximum angle of carpal flexion, heart rate, systolic arterial pressure, respiratory rate, temperature, and intestinal motility were evaluated before LPS injection (baseline), 6 h after LPS injection (time 0), and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 h after treatments. Although the model of synovitis produced clear clinical signs of inflammation, the lameness scores in group C were different from the baseline for only up to 12 h. Both morphine and buprenorphine showed a reduction in the degree of lameness starting at 0.5 and 6 h, respectively. Reduced intestinal motility was observed at 0.5 h in group M and at 0.5 to 1 h in group B. Epidural morphine was a more effective analgesic that lasted for more than 12 h and without side effects. It was concluded that morphine would be a valuable analgesic option to alleviate joint pain in the thoracic limbs in ponies.

  20. Sexual Dysfunction in Heroin Dependents: A Comparison between Methadone and Buprenorphine Maintenance Treatment.

    Directory of Open Access Journals (Sweden)

    Anne Yee

    Full Text Available Methadone has long been regarded as an effective treatment for opioid dependence. However, many patients discontinue maintenance therapy because of its side effects, with one of the most common being sexual dysfunction. Buprenorphine is a proven alternative to methadone. This study aimed to investigate sexual dysfunction in opioid-dependent men on buprenorphine maintenance treatment (BMT and methadone maintenance treatment (MMT. The secondary aim was to investigate the correlation between sexual dysfunction and the quality of life in these patients.Two hundred thirty-eight men participated in this cross-sectional study. Four questionnaires were used, the Mini International Neuropsychiatric Interview, Opiate Treatment Index, Malay version of the International Index of Erectile Function 15 (Mal-IIEF-15, and World Health Organization Quality of Life-BREF Scale. Multivariate analysis of covariance was used to examine the relationship between MMT and BMT and the Mal-IIEF 15 scores while controlling for all the possible confounders.The study population consisted of 171 patients (71.8% on MMT and 67 (28.2% on BMT. Patients in the MMT group who had a sexual partner scored significantly lower in the sexual desire domain (p < 0.012 and overall satisfaction (p = 0.043 domain compared with their counterparts in the BMT group. Similarly, patients in the MMT group without a sexual partner scored significantly lower in the orgasmic function domain (p = 0.008 compared with those in the BMT group without a partner. Intercourse satisfaction (p = 0.026 and overall satisfaction (p = 0.039 were significantly associated with the social relationships domain after adjusting for significantly correlated sociodemographic variables.Sexual functioning is critical for improving the quality of life in patients in an opioid rehabilitation program. Our study showed that buprenorphine causes less sexual dysfunction than methadone. Thus, clinicians may consider the former when

  1. Post operative analgesia after incisional infiltration of bupivacaine v/s bupivacaine with buprenorphine

    Directory of Open Access Journals (Sweden)

    Tanu R Mehta

    2011-01-01

    Full Text Available Introduction: Opioid receptors have been demonstrated in the peripheral nerve endings of afferent neurons. Blockade of these receptors with peripherally administered opioid is believed to result in analgesia. Aim: To evaluate whether buprenorphine added to bupivacaine for wound infiltration can enhance post-operative analgesia via peripheral mechanisms. Materials and Methods: Forty ASA I and II adult patients scheduled for open donor nephrectomy were enrolled in this randomized double blind prospective study. In group A ( n=20 patients, the wound was infiltrated with bupivacaine 0.5% (2 mg/kg and in group B ( n=20 with bupivacaine 0.5% (2 mg/kg and buprenorphine (2 μg/kg. All patients were given diclofenac 75 mg IM at 8 h interval. Post-operative quality of analgesia was assessed by VAS (0-10 for 24 h and when VAS > 4 rescue analgesic was administered. Total dose of rescue analgesic and side effects were noted. Results: The time of administration of first rescue analgesic was significantly higher in group B (10.52±5.54 h as compared to group A (3.275±1.8 h. Mean VAS was significantly lower in group B as compared to group A. The total dosage of rescue analgesic was more in group A as compared to group B patients. Conclusion: Addition of buprenorphine to the local anesthetic significantly prolonged the time to first rescue analgesic requirement and the total consumption of rescue analgesic in 24 h, thus providing evidence in support of the existence of peripheral opioid receptors.

  2. COMPARISON OF DEXMEDETOMIDINE, BUPRENORPHINE AND FENTANYL AS AN ADJUVANT TO BUPIVACAINE DURING SPINAL ANAESTHESIA FOR HEMIARTHROPLASTY

    Directory of Open Access Journals (Sweden)

    Pradeep R

    2016-10-01

    Full Text Available BACKGROUND Opioids such as fentanyl or buprenorphine are being added as adjuvant to local anaesthetic for spinal anaesthesia. Dexmedetomidine, a new α2 agonist is being tried as an adjuvant in the recent times. MATERIALS AND METHODS The patients were randomised into three Groups (n=30 each by closed envelope technique. Patients in Group 1 received 10 µg fentanyl with 15 mg of 0.5% hyperbaric bupivacaine, Group 2 received 15 mg of 0.5% hyperbaric bupivacaine supplemented with 30 µg of buprenorphine and Group 3 received 15 mg of 0.5% hyperbaric bupivacaine plus 5 µg dexmedetomidine intrathecally. The time to reach maximum sensory and motor level, the regression time of the same, any adverse effects were recorded. Data were analysed using chi-square test or Fisher’s exact test for categorical data and analysis of variance for continuous data. A value of P<0.05 was accepted as statistically significant. Settings and Design- The study was conducted in a prospective, randomised and double-blind manner. It included ninety American Society of Anaesthesiologists class I and II patients undergoing hemiarthroplasty under spinal anaesthesia. RESULTS In this study, the patients in dexmedetomidine group showed significantly longer duration of motor block (240±20 mins. and sensory blockade (180±22.2 mins. compared to other groups, which is statistically significant (P=0.0001 and P=0.006, respectively. The time to first request of analgesic postoperatively was also longer (260±30.2 in dexmedetomidine group when compared with other groups (P=0.0001. Haemodynamic parameters were stable and there were no complications in any group. CONCLUSIONS We concluded that intrathecal dexmedetomidine (5 µg with bupivacaine provides significantly longer duration of sensory and motor blockade and longer duration for first request of analgesia in the recovery than intrathecal buprenorphine (30 µg or fentanyl (10 µg with bupivacaine for spinal anaesthesia for

  3. Impact of a prescription monitoring program on doctor-shopping for high dosage buprenorphine.

    Science.gov (United States)

    Pradel, Vincent; Frauger, Elisabeth; Thirion, Xavier; Ronfle, Eléonore; Lapierre, Véronique; Masut, Alain; Coudert, Christine; Blin, Olivier; Micallef, Joëlle

    2009-01-01

    Doctor-shopping (simultaneous use of several physicians by a patient) is one of the most frequent ways of diversion for prescription drugs. A specific method was used to assess the evolution of doctor-shopping for High Dosage Buprenorphine (HDB) in a French region from 2000 to 2005 and the impact of a prescription monitoring program for HDB implemented in 2004. Data from eight periods (semesters of years 2000, 2002, 2004, and 2005) were extracted from a prescription database. Three quantities (the delivered, the prescribed, and the doctor-shopping quantity) were computed for each patient. The total doctor-shopping quantity and the doctor-shopping ratio (percentage of buprenorphine obtained through doctor-shopping) were used to evaluate the diversion of HDB among the population. The total prescribed quantity and the number of patients treated regularly were used as indicators of the access to treatment. The doctor-shopping ratio increased from 1st semester 2000 to 1st semester 2004 (from 14.9 to 21.7%) and then decreased to 16.9% in 2nd semester 2005. The total doctor-shopping quantity followed the same evolution. The number of patients treated remained stable from 1st semester 2000 to 2nd semester 2005. The prescribed quantity increased from 1st semester 2000 to 2nd semester 2002, decreased in 1st semester 2004 (4163 g) and then remained stable. After a four-year increase of the diversion through doctor-shopping for buprenorphine the beginning of the prescription monitoring program was concomitant with a marked decrease of doctor-shopping indicators without notable impact on the access to treatment.

  4. Clinician recommendation of 12-step meeting attendance and discussion regarding disclosure of buprenorphine use among patients in office-based opioid treatment.

    Science.gov (United States)

    Suzuki, Joji; Dodds, Tyler

    2016-01-01

    Clinicians are encouraged to include 12-step meetings, such as Alcoholics or Narcotics Anonymous (AA/NA), as ancillary services for the treatment for opioid use disorders (OUDs), even though some of these groups may not fully accept individuals receiving buprenorphine. Little is known about whether clinicians actually discuss with patients the issue of disclosure of buprenorphine use at 12-step meetings. An anonymous survey was offered to patients enrolled in office-based opioid treatment with buprenorphine to assess whether their clinicians recommended attendance at 12-step meetings and discussed the issue of disclosing their use of buprenorphine to other members. The patients' attendance at 12-step meetings was also assessed, as well as beliefs and prior experiences related to disclosure of buprenorphine use at 12-step meetings. Thirty patients completed the survey. Twenty-one respondents (75.0%) indicated that they were encouraged to attend meetings, but only 9 (33.3%) reported having any discussion with their clinicians about the issue of disclosing their use of buprenorphine at meetings. The majority (76.7%) reported attending 12-step meetings at least occasionally, and 70% reported finding the meetings helpful. Nearly one third (30%) expressed concerns that other 12-step members would not accept them if their buprenorphine status were known, and a similar proportion (37%) frequently avoided disclosing their use of buprenorphine. Clinicians recommended 12-step meetings to most patients but did not routinely discuss issues of disclosure. Despite utilizing 12-step meetings and reporting them to be helpful, many avoided disclosing their use of buprenorphine to others. More research is needed to better understand how clinicians may assist patients to best utilize 12-step meetings.

  5. Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus)

    OpenAIRE

    Taylor, Bryan F; Ramirez, Harvey E.; Battles, August H; Andrutis, Karl A.; Neubert, John K.

    2016-01-01

    Effective pain management for rats and mice is crucial due to the continuing increase in the use of these species in biomedical research. Here we used a recently validated operant orofacial pain assay to determine dose–response curves for buprenorphine and tramadol when mixed in nut paste and administered to male and female rats. Statistically significant analgesic doses of tramadol in nut paste included doses of 20, 30, and 40 mg/kg for female rats but only 40 mg/kg for male rats. For male r...

  6. Comparison of bupivacaine, xylazine and buprenorphine with ketamine combination for spinal analgesia in buffalo calves

    Directory of Open Access Journals (Sweden)

    Rekha Pathak

    Full Text Available Aim: The study was undertaken to compare the clinical efficacy of lumbosacral spinal analgesia produced using bupivacaine, xylazine and buprenorphine with ketamine combination in buffalo calves. Materials and Methods: 36 male buffalo calves of seven to eight months of age and weighing 60 to 75 kg were used to evaluate the efficacy and safety of lumbosacral spinal analgesia produced by bupivacaine 0.25mg/kg, xylazine 0.05 mg/kg and buprenorphine 20 μg/kg in combination with ketamine 2.5mg/ kg and divided into groups A, B and C, respectively with 12 animals in each group. Results: The onset of analgesia in animals of group A (bupivacaine + ketamine was 3.0±0.3 min, group B (xylazine + ketamine was recorded as 2.6±0.4 min and group C (buprenorphine + ketamine 4.0±0.4 min. Ketamine-bupivacaine in animals of group A produced complete analgesia of almost all the dermatomes for varying lengths of time. So also the group B except that it produced only moderate analgesia of thorax, abdomen and flank. Animals of group C produced only mild analgesia of thorax, abdomen and flank and moderate analgesia of digits , perineum, inguinal, himd limbs and tail region. The longest (>180 min. duration of complete analgesia was recorded in animals of group A. The heart rate and respiration rate significantly decreased in group A and B than group C, so also the rectal temperature. Sedation recorded was maximum in group B fallowed by group A and least sedation scores were given by group C animals. Similiarly the scores of motor incordination was higher in group B and group A than group C. Conclusion: It was concluded that the combinations viz. Bupivacaine+ Ketamine and Xylazine + ketamine when given intraspinally at the lumbosacral space have similar analgesic potency on spinal administration in buffaloes. The synergism is more pronounced in xylazine-ketamine combination,whereas Buprenorphine +ketamine combination in the above said dose is a poor analgesic agent

  7. Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats

    OpenAIRE

    Guarnieri, M.; Brayton, C.; Sarabia-Estrada, R.; Tyler, B.; McKnight, P.; DeTolla, L.

    2017-01-01

    A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The s...

  8. Hemodynamic and Behavioral Differences after Administration of Meloxicam, Buprenorphine, or Tramadol as Analgesics for Telemeter Implantation in Mice

    Science.gov (United States)

    Rätsep, Matthew T; Barrette, Valerie F; Winterborn, Andrew; Adams, Michael A; Croy, B Anne

    2013-01-01

    Cannulation of the common carotid artery for chronic, continuous radiotelemetric recording of aortic hemodynamic properties in mice is a highly invasive recovery surgery. Radiotelemetric recording, by its continuous nature, gives the most accurate measurements of hemodynamic variables in experimental animals, and is widely used in the study of cardiovascular diseases including hypertension. The American Heart Association has recommended data acquisition by radiotelemetric recording but did not provide guidelines regarding postoperative analgesic support. We assessed hemodynamic parameters, locomotor activity, food intake, and weight loss in radiotransmitter-implanted CD1 female mice receiving analgesic support during the first 48 h after surgery. The efficacy of analgesic support from the NSAID meloxicam was compared with that of the widely used opioid agonist buprenorphine and the related compound, tramadol. Meloxicam-treated mice recovered lost body weight more rapidly than did tramadol- or buprenorphine-treated mice. Furthermore, meloxicam-treated mice maintained circadian rhythm after surgery and had tighter regulation of mean arterial pressure than did tramadol- or buprenorphine-treated mice. Meloxicam was also superior with regard to food intake, locomotor activity, and limiting variance in hemodynamic parameters. This study indicates that when compared with buprenorphine and tramadol, meloxicam should be the postoperative analgesic of choice for radiotelemeter implantation in mice. PMID:24041211

  9. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40

    Science.gov (United States)

    Boone, Margaret; Brown, Nancy J.; Moon, Mary A.; Schuman, Deborah J.; Thomas, Josephine; Wright, Denise L.

    2004-01-01

    This Treatment Improvement Protocol (TIP) addresses the clinical use of buprenorphine in the treatment of opioid addiction. TIPs are best-practice guidelines for the treatment of substance use disorders that make the latest research in substance abuse treatment available to counselors and educators. The content was generated by a panel of experts…

  10. Switching from high doses of pure μ-opioid agonists to transdermal buprenorphine in patients with cancer

    DEFF Research Database (Denmark)

    Lundorff, Lena; Sjøgren, Per; Hansen, Ole Bo

    2013-01-01

    BACKGROUND: Several myths on buprenorphine's pharmacology exist: possible analgesic ceiling effect, feasibility of combination with other opioid agonists, and the reversibility of side effects. Aim to evaluate: 1) if cancer patients receiving high doses of pure agonists could obtain adequate pain...

  11. A prospective multi-centre clinical trial to compare buprenorphine and butorphanol for postoperative analgesia in cats.

    Science.gov (United States)

    Taylor, Polly M; Kirby, Jonathan J; Robinson, Clare; Watkins, Elizabeth A; Clarke, David D; Ford, Marion A; Church, Karen E

    2010-04-01

    One hundred and fifty-three cats undergoing surgery in seven veterinary practices in Great Britain were studied. They were randomly allocated to receive either 10-20 microg/kg buprenorphine or 0.4 mg/kg butorphanol with acepromazine before anaesthesia with propofol, Saffan or thiopentone and isoflurane or halothane. Routine monitoring was undertaken. Pain and sedation were assessed blind using a four point (0-3) simple descriptive scale (SDS) at 1, 2, 4, 8 and 24h. Pain and sedation data were compared using non-parametric statistical tests and continuous data using t tests or analysis of variance (ANOVA). Anaesthesia and surgery were uneventful, and cardiorespiratory data were within normal limits. After surgery, overall, more cats had pain score 0 after buprenorphine and more had pain score 3 after butorphanol (P=0.0465). At individual time points, more cats had lower pain scores after buprenorphine at 2 (P=0.040) and 24 (P=0.036)h. At 24h 83% after buprenorphine and 63% after butorphanol had pain score 0 (PBuprenorphine provided better and longer lasting postoperative analgesia than butorphanol. Copyright 2009 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

  12. A Review of Buprenorphine Diversion and Misuse: The Current Evidence Base and Experiences from Around the World

    Science.gov (United States)

    Lofwall, Michelle R.; Walsh, Sharon L.

    2014-01-01

    Outpatient opioid addiction treatment with sublingual buprenorphine pharmacotherapy (OBOT) has rapidly expanded in the United States and abroad, and, with this increase in medication availability, there have been increasing concerns about its diversion, misuse and related harms. This narrative review defines the behaviors of diversion and misuse, examines how the pharmacology of buprenorphine alone and in combination with naloxone influence its abuse liability, and describes the epidemiological data on buprenorphine diversion and intravenous misuse, risk factors for its intravenous misuse and the unintended consequences of misuse and diversion. Physician practices to prevent, screen for, and therapeutically respond to these behaviors, which are a form of medication non-adherence, are discussed and gaps in knowledge are identified. OBOT experiences from other countries that have varied health care systems, public policies, and access to addiction treatment are shared in order to make clear that diversion and misuse occur across the world in various contexts, for many different reasons, and are not limited to buprenorphine. Comparisons are made with other opioids with known abuse liability as well as medications with no known abuse. The objective is to facilitate understanding of diversion and misuse so that all factors influencing their expression (patient and provider characteristics and public policy) can be appreciated within a framework that also recognizes the benefits of addiction treatment. With this comprehensive perspective, further careful work can help determine how to minimize these behaviors without eroding the current benefits realized through improved addiction treatment access and expansion. PMID:25221984

  13. Predictors of Abstinence: National Institute of Drug Abuse Multisite Buprenorphine/Naloxone Treatment Trial in Opioid-Dependent Youth

    Science.gov (United States)

    Subramaniam, Geetha A.; Warden, Diane; Minhajuddin, Abu; Fishman, Marc J.; Stitzer, Maxine L.; Adinoff, Bryon; Trivedi, Madhukar; Weiss, Roger; Potter, Jennifer; Poole, Sabrina A.; Woody, George E.

    2011-01-01

    Objective: To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal)-assisted psychosocial treatment for opioid-dependent youth. Method: Secondary analyses were performed of data from 152 youth (15-21 years old) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification with weekly…

  14. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery

    Directory of Open Access Journals (Sweden)

    Ghasem Soltani

    2015-10-01

    Full Text Available Background: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient’s satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. Methods: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They were older than 18 years and in classes I and II of the American Society of Anesthesiologists (ASA with an operation time of 30-90 minutes. Patients were divided into two groups of buprenorphine (4.5μg/kg sublingually and morphine (0.2mg/kg intravenously. Baseline characteristics, vital signs, pain score, level of sedation and pharmacological side effects were recorded in the recovery room (at 0 and 30 minutes, and in the ward (at 3, 6 and 12 hours. SPSS version 19 software was used for data analysis and the significance level was set at P Results: Ninety patients were studied, 60 males and 30 females with a mean age of 37.7±16.2 years. There was no significant difference between the two groups in terms of baseline characteristics.Pain score in the morphine group was significantly higher than the buprenorphine group with an average score of 2.5 (P

  15. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery

    Directory of Open Access Journals (Sweden)

    Ghasem Soltani

    2015-09-01

    Full Text Available Background: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient’s satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. Methods: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They were older than 18 years and in classes I and II of the American Society of Anesthesiologists (ASA with an operation time of 30-90 minutes. Patients were divided into two groups of buprenorphine (4.5μg/kg sublingually and morphine (0.2mg/kg intravenously. Baseline characteristics, vital signs, pain score, level of sedation and pharmacological side effects were recorded in the recovery room (at 0 and 30 minutes, and in the ward (at 3, 6 and 12 hours. SPSS version 19 software was used for data analysis and the significance level was set at P Results: Ninety patients were studied, 60 males and 30 females with a mean age of 37.7±16.2 years. There was no significant difference between the two groups in terms of baseline characteristics.Pain score in the morphine group was significantly higher than the buprenorphine group with an average score of 2.5 (P

  16. Results of a pilot randomized controlled trial of buprenorphine for opioid dependent women in the criminal justice system.

    Science.gov (United States)

    Cropsey, Karen L; Lane, Peter S; Hale, Galen J; Jackson, Dorothy O; Clark, C Brendan; Ingersoll, Karen S; Islam, M Aminul; Stitzer, Maxine L

    2011-12-15

    Recent studies have demonstrated the efficacy of both methadone and buprenorphine when used with opioid dependent men transitioning from prison to the community, but no studies have been conducted with women in the criminal justice (CJ) system. The aim of this study was to determine the efficacy of buprenorphine for relapse prevention among opioid dependent women in the CJ system transitioning back to the community. 36 women under CJ supervision were recruited from an inpatient drug treatment facility that treats CJ individuals returning back to the community. Nine were enrolled in an open label buprenorphine arm then 27 were randomized to buprenorphine (n=15) or placebo (n=12; double-blind). All women completed baseline measures and started study medication prior to release. Participants were followed weekly, provided urine drug screens (UDS), received study medication for 12 weeks, and returned for a 3-month follow-up. Intent-to-treat analyses were performed for all time points through 3 month follow-up. The majority of participants were Caucasian (88.9%), young (M±SD=31.8±8.4 years), divorced/separated (59.2%) women with at least a high school/GED education (M±SD=12±1.7 years). GEE analyses showed that buprenorphine was efficacious in maintaining abstinence across time compared to placebo. At end of treatment, 92% of placebo and 33% of active medication participants were positive for opiates on urine drug screen (Chi-Square=10.9, df=1; pup point, no differences were found between the two groups, with 83% of participants at follow-up positive for opiates. Women in the CJ system who received buprenorphine prior to release from a treatment facility had fewer opiate positive UDS through the 12 weeks of treatment compared to women receiving placebo. Initiating buprenorphine in a controlled environment prior to release appears to be a viable strategy to reduce opiate use when transitioning back to the community. Copyright © 2011 Elsevier Ireland Ltd. All rights

  17. Urine analysis of buprenorphine/norbuprenorphine/ naloxone in drugs and driving cases

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    Albert A. Elian

    2015-07-01

    Full Text Available Buprenorphine is now being detected as a drug of abuse in drugs/driving cases alongside side naloxone. Being a semi synthetic opiate, it has the potential to impair motorists in a similar fashion to morphine. Many laboratories have observed that buprenorphine does not produce a positive response with typical opiate immunoassays or routine basic GC-MS drug screens. In this study, samples of urine were enzymatically hydrolyzed after which they were extracted on mixed mode solid phase (SPE columns, after which the extracted samples were analyzed by LC-MS/MS analysis in positive multiple reaction monitoring mode. The LOD/LOQ were determined to be 0.5 and 1.0 ng/mL, respectively for the analytes; linearity (10 to 1000 ng/mL and (r2>0.999. The recovery of the analytes was found to be greater than 90%. Interday/intraday analysis was found to <8% and <10%, respectively. Matrix effects were determined to be <6%.

  18. Subcutaneous Implants of a Cholesterol-Triglyceride-Buprenorphine Suspension in Rats

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    M. Guarnieri

    2017-01-01

    Full Text Available A Target Animal Safety protocol was used to examine adverse events in male and female Fischer F344/NTac rats treated with increasing doses of a subcutaneous implant of a lipid suspension of buprenorphine. A single injection of 0.65 mg/kg afforded clinically significant blood levels of drug for 3 days. Chemistry, hematology, coagulation, and urinalysis values with 2- to 10-fold excess doses of the drug-lipid suspension were within normal limits. Histopathology findings were unremarkable. The skin and underlying tissue surrounding the drug injection were unremarkable. Approximately 25% of a cohort of rats given the excess doses of 1.3, 3.9, and 6.5 mg/kg displayed nausea-related behavior consisting of intermittent and limited excess grooming and self-gnawing. These results confirm the safety of cholesterol-triglyceride carrier systems for subcutaneous drug delivery of buprenorphine in laboratory animals and further demonstrate the utility of lipid-based carriers as scaffolds for subcutaneous, long-acting drug therapy.

  19. The barriers to smoking cessation in Swiss methadone and buprenorphine-maintained patients

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    Stohler Rudolf

    2008-03-01

    Full Text Available Abstract Background Smoking rates in methadone-maintained patients are almost three times higher than in the general population and remain elevated and stable. Due to the various negative health effects of smoking, nicotine dependence contributes to the high mortality in this patient group. The purpose of the current study was to investigate Swiss methadone and buprenorphine-maintained patients' willingness to stop smoking and to clarify further smoking cessation procedures. Methods Substance abuse history, nicotine dependence, and readiness to stop smoking were assessed in a sample of 103 opiate-dependent patients in the metropolitan area of Zurich, Switzerland. Patients were asked to document their smoking patterns and readiness to quit. Results Only a small number of patients were willing to quit smoking cigarettes (10.7% and, even though bupropione or nicotine replacement therapy was included in the fixed daily treatment care, only one patient received nicotine replacement therapy for smoking cessation. A diagnosis of depression in patients' clinical records was associated with readiness to stop smoking. No significant associations were found between readiness to quit smoking and age, methadone treatment characteristics, and presence of co-dependencies. Conclusion The current prescription level of best medicine for nicotine dependence in Swiss methadone and buprenorphine-maintained patients is far from adequate. Possible explanations and treatment-relevant implications are discussed.

  20. Considerations on the role of buprenorphine in recovery from heroin addiction from a UK perspective.

    Science.gov (United States)

    Nutt, David J

    2015-01-01

    The United Kingdom Drug Strategy emphasises recovery as a key focus in the treatment of drug dependence. A framework for recovery is defined in the Recovery-Orientated Drug Treatment report, written by an expert working group, and comprises four key phases: engagement and stabilisation, including the establishment of treatment goals; preparation for change, involving engagement in psychosocial and pharmacological interventions; active change, including detoxification and medical withdrawal; and completion, including interventions that strengthen community integration. A body of evidence supports the benefits of buprenorphine, a partial agonist at mu opioid receptors, in supporting individualised recovery based on this framework, specifically in relation to the potential for rapid stabilisation, flexibility to transition to other treatment options or achieve abstinence, effective blocking of on-top use of illicit drugs, the treatment of comorbidities through the minimisation of drug-drug interactions, and a good safety profile. In addition, the newer abuse-deterrent formulation of buprenorphine combined with the opioid antagonist naloxone is likely to strengthen recovery-orientated systems of care due to its potential to reduce misuse and diversion. Progress through the recovery journey and the ability to sustain recovery will depend on individual needs and goals and on the amount of recovery capital that individuals have developed. © The Author(s) 2014.

  1. Buprenorphine signalling is compromised at the N40D polymorphism of the human μ opioid receptor in vitro.

    Science.gov (United States)

    Knapman, Alisa; Santiago, Marina; Connor, Mark

    2014-09-01

    There is significant variation in individual response to opioid drugs, which may result in inappropriate opioid therapy. Polymorphisms of the μ opioid receptor (MOP receptor) may contribute to individual variation in opioid response by affecting receptor function, and the effect may be ligand-specific. We sought to determine functional differences in MOP receptor signalling at several signalling pathways using a range of structurally distinct opioid ligands in cells expressing wild-type MOP receptors (MOPr-WT) and the commonly occurring MOP receptor variant, N40D. MOPr-WT and MOPr-N40D were stably expressed in CHO cells and in AtT-20 cells. Assays of AC inhibition and ERK1/2 phosphorylation were performed on CHO cells, and assays of K activation were performed on AtT-20 cells. Signalling profiles for each ligand were compared between variants. Buprenorphine efficacy was reduced by over 50% at MOPr-N40D for AC inhibition and ERK1/2 phosphorylation. Buprenorphine potency was reduced threefold at MOPr-N40D for K channel activation. Pentazocine efficacy was reduced by 50% for G-protein-gated inwardly rectifying K channel activation at MOPr-N40D. No other differences were observed for any other ligands tested. The N40D variant is present in 10-50% of the population. Buprenorphine is a commonly prescribed opioid analgesic, and many individuals do not respond to buprenorphine therapy. This study demonstrates that buprenorphine signalling to several effectors via the N40D variant of MOP receptors is impaired, and this may have important consequences in a clinical setting for individuals carrying the N40D allele. © 2014 The British Pharmacological Society.

  2. Efficacy of oral transmucosal and intravenous administration of buprenorphine before surgery for postoperative analgesia in dogs undergoing ovariohysterectomy.

    Science.gov (United States)

    Ko, Jeff C; Freeman, Lynetta J; Barletta, Michele; Weil, Ann B; Payton, Mark E; Johnson, Brenda M; Inoue, Tomohito

    2011-02-01

    To compare the efficacy of preoperative administration of buprenorphine (via oral transmucosal [OTM] and IV routes) for postoperative analgesia in dogs undergoing ovariohysterectomy. Prospective, randomized, blinded study. 18 dogs undergoing routine ovariohysterectomy. Dogs were allocated to 3 groups (6 dogs/group) and were assigned to receive buprenorphine (20 μg/kg [9.09 μg/lb], IV; a low dose [20 μg/kg] via OTM administration [LOTM]; or a high dose [120 μg/kg [54.54 μg/lb] via OTM administration [HOTM]) immediately before anesthetic induction with propofol and maintenance with isoflurane for ovariohysterectomy. Postoperative pain was assessed by use of a dynamic interactive pain scale. Dogs were provided rescue analgesia when postoperative pain exceeded a predetermined threshold. Blood samples were collected, and liquid chromatography-electrospray ionization-tandem mass spectrometry was used to determine plasma concentrations of buprenorphine and its metabolites. Data were analyzed with an ANOVA. Body weight, surgical duration, propofol dose, isoflurane concentration, and cardiorespiratory variables did not differ significantly among treatment groups. Number of dogs requiring rescue analgesia did not differ significantly for the HOTM (1/6), IV (3/6), and LOTM (5/6) treatments. Similarly, mean ± SEM duration of analgesia did not differ significantly for the HOTM (20.3 ± 3.7 hours), IV (16.0 ± 3.8 hours), and LOTM (7.3 ± 3.3 hours) treatments. Plasma buprenorphine concentration was ≤ 0.60 ng/mL in 7 of 9 dogs requiring rescue analgesia. Buprenorphine (HOTM) given immediately before anesthetic induction can be an alternative for postoperative pain management in dogs undergoing ovariohysterectomy.

  3. Management of eight labor and delivery patients dependent on buprenorphine (Subutex™: A retrospective chart review [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Solina Tith

    2018-02-01

    Full Text Available Background: Opioid use during pregnancy is a growing concern in the United States. Buprenorphine has been recommended by “The American College of Obstetrics and Gynecology” as an alternative to methadone to decrease risks associated with the use of illicit opioids during pregnancy. The partial μ-opioid agonists’ unique pharmacology, including its long half time and high affinity to the μ-opioid receptor, complicates patient management in a highly kinetic, and often urgent field like obstetric anesthesia. We reviewed our management and outcomes in this medically complex population. Methods: An Institutional Review Board (IRB approved retrospective chart review was conducted of women admitted to the University of Washington Medical Center Labor and Delivery unit from July 2012 to November 2013 using buprenorphine. All deliveries, including intrauterine fetal demise, were included. Results: Eight women were admitted during this period to our L&D floor on buprenorphine. All required peri-partum anesthetic management either for labor and/or cesarean delivery management. Analgesic management included dilaudid or fentanyl PCA and/or continued epidural infusion, and in one instance ketamine infusion, while the pre-admission buprenorphine regimen was continued. Five babies were viable, two women experienced intrauterine fetal death at 22 and 36 weeks gestational age (GSA, respectively, and one neonate died shortly after delivery due to a congenital diaphragmatic hernia. Conclusions: This case series illuminates the medical complexity of parturients using buprenorphine. Different treatment modalities in the absence of evidence-based guidelines included additional opioid administration and continued epidural analgesia. The management of post-cesarean pain in patients on partial μ-opioid agonists remains complex and variable, and evidence-based guidelines could be useful for clinicians to direct care.

  4. States' implementation of the Affordable Care Act and the supply of physicians waivered to prescribe buprenorphine for opioid dependence.

    Science.gov (United States)

    Knudsen, Hannah K; Lofwall, Michelle R; Havens, Jennifer R; Walsh, Sharon L

    2015-12-01

    Although the Affordable Care Act (ACA) is anticipated to affect substance use disorder (SUD) treatment, its impact on the supply of physicians waivered to treat opioid dependence with buprenorphine has not been considered. This study examined whether states more supportive of ACA, meaning those that had opted to expand Medicaid and establish a state-based health insurance exchange, experienced greater growth in physician supply than less supportive states. Buprenorphine physician supply, including total physician supply, supply of 30-patient physicians, and supply of 100-patient physicians per 100,000 state residents, was measured from June 2013 to May 2015. State characteristics were drawn from multiple secondary sources, with states categorized as ACA-supportive, ACA-hybrid (where states either expanded Medicaid or established a state-based exchange), or ACA-resistant (where states took neither action). Mixed effects regression was used to estimate state-level growth curves to test whether rates of growth varied by states' approaches to implementing ACA. The supply of waivered physicians grew significantly over the two-year period. Rates of growth were significantly lower in ACA-hybrid and ACA-resistant states relative to growth in ACA-supportive states. Average buprenorphine physician supply at baseline varied by region, the percentage of residents covered by Medicaid, and the supply of specialty SUD treatment programs. This study found a positive impact of the ACA on growth in the supply of buprenorphine-waivered physicians in US states. Future research should address whether the ACA affects the number of patients receiving buprenorphine, Medicaid spending, and the quality of treatment services delivered. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Benzodiazepine use among opiate-dependent subjects in buprenorphine maintenance treatment: correlates of use, abuse and dependence.

    Science.gov (United States)

    Lavie, Estelle; Fatséas, Mélina; Denis, Cécile; Auriacombe, Marc

    2009-01-01

    Previous studies from North America, Europe and Australia have reported high levels of benzodiazepine use among opiate-dependent patients in opiate maintenance treatment. However, to date, there are no available data on patterns of abuse and dependence on benzodiazepines according to DSM criteria among these patients. To describe the independent correlates of use, abuse and dependence on benzodiazepines among buprenorphine patients selected from standard treatment settings. Cross-sectional study in France between June 2001 and June 2004. Buprenorphine patients treated for over 3 months were recruited via physicians prescribing buprenorphine. Patients answered a self-administered questionnaire, the DSM-IV criteria for benzodiazepine abuse and dependence, the Beck Anxiety and Depression Inventories (BAI, BDI) and the Nottingham Health Profile (NHP). Main outcome was modalities of benzodiazepine use: no use vs. simple use vs. problematic use (abuse or dependence according to DSM-IV). 170 patients were recruited. 54% did not use benzodiazepines during the previous month, 15% were simple users and 31% were problematic users. Benzodiazepine use (all modalities) was associated with poly-use of psychotropics. Simple users of benzodiazepines were not statistically different from non-users for the other factors explored. Problematic users of benzodiazepines had higher depression and anxiety levels, correlated with quality of life impairment and precariousness. They used higher dosages of benzodiazepines than simple users. Characteristics of simple benzodiazepine users were distinct from problematic users but not from non-users in this sample of buprenorphine patients. This should be taken into account in the clinical management of benzodiazepine use among buprenorphine patients.

  6. Roles of μ-Opioid Receptors and Nociceptin/Orphanin FQ Peptide Receptors in Buprenorphine-Induced Physiological Responses in Primates

    Science.gov (United States)

    Cremeans, Colette M.; Gruley, Erin; Kyle, Donald J.

    2012-01-01

    Buprenorphine is known as a μ-opioid peptide (MOP) receptor agonist, but its antinociception is compromised by the activation of nociceptin/orphanin FQ peptide (NOP) receptors in rodents. The aim of this study was to investigate the roles of MOP and NOP receptors in regulating buprenorphine-induced physiological responses in primates (rhesus monkeys). The effects of MOP antagonist (naltrexone), NOP antagonist [(±)-1-[(3R*,4R*)-1-(cyclooctylmethyl)-3-(hydroxymethyl)-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397)], and NOP agonists [(1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4.5] decan-4-one (Ro 64-6198) and 3-endo-8-[bis(2-methylphenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol (SCH 221510)] on buprenorphine were studied in three functional assays for measuring analgesia, respiratory depression, and itch in primates. Over the dose range of 0.01 to 0.1 mg/kg, buprenorphine dose-dependently produced antinociception, respiratory depression, and itch/scratching responses, and there was a ceiling effect at higher doses (0.1–1 mg/kg). Naltrexone (0.03 mg/kg) produced similar degrees of rightward shifts of buprenorphine's dose-response curves for all three endpoints. Mean pKB values of naltrexone (8.1–8.3) confirmed that MOP receptors mediated mainly buprenorphine-induced antinociception, respiratory depression, and itch/scratching. In contrast, J-113397 (0.1 mg/kg) did not change buprenorphine-induced physiological responses, indicating that there were no functional NOP receptors in buprenorphine-induced effects. More importantly, both NOP agonists, Ro 64-6198 and SCH 221510, enhanced buprenorphine-induced antinociception without respiratory depression and itch/ scratching. The dose-addition analysis revealed that buprenorphine in combination with the NOP agonist synergistically produced antinociceptive effects. These findings provided functional evidence that the activation of NOP receptors did not

  7. Inhibition of glucuronidation and oxidative metabolism of buprenorphine using GRAS compounds or dietary constituents/supplements: in vitro proof of concept.

    Science.gov (United States)

    Maharao, Neha V; Joshi, Anand A; Gerk, Phillip M

    2017-03-01

    The present study investigated the potential of generally recognized as safe (GRAS) compounds or dietary substances to inhibit the presystemic metabolism of buprenorphine and to increase its oral bioavailability. Using IVIVE, buprenorphine extraction ratios in intestine and liver were predicted as 96% and 71%, respectively. In addition, the relative fraction of buprenorphine metabolized by oxidation and glucuronidation in these two organs was estimated using pooled human intestinal and liver microsomes. In both organs, oxidation appeared to be the major metabolic pathway with a 6 and 4 fold higher intrinsic clearance than glucuronidation in intestine and liver, respectively. The oral bioavailability of buprenorphine was predicted to be 1.16%. Inhibition of 75% and 50% of intestinal and hepatic presystemic metabolism would result in an F oral of 49%, which is comparable to the bioavailability of sublingual buprenorphine. In human liver microsomes, chrysin, curcumin, ginger extract, hesperitin, magnolol, quercetin and silybin inhibited ≥50% glucuronidation, whereas chrysin, curcumin, ginger extract, 6-gingerol, pterostilbene, resveratrol and silybin exhibited ≥30% inhibition of oxidation. In human intestinal microsomes, curcumin, ginger extract, α-mangostin, quercetin and silybin inhibited ≥50% glucuronidation while chrysin, ginger extract, α-mangostin, pterostilbene and resveratrol exhibited ≥30% inhibition of oxidation. These results demonstrate the feasibility of our proposed approach of using GRAS or dietary compounds to inhibit the presystemic metabolism of buprenorphine and thus improve its oral bioavailability. An oral buprenorphine formulation containing these inhibitors or their combinations has promising potential to replace sublingual buprenorphine. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  8. A multicentre, prospective, randomised, blinded clinical trial to compare some perioperative effects of buprenorphine or butorphanol premedication before equine elective general anaesthesia and surgery

    OpenAIRE

    Taylor, P. M.; Hoare, H. R.; de Vries, A.; Love, E. J.; Coumbe, K. M.; White, KL; Murrell, J. C.

    2016-01-01

    Reasons for performing study: Buprenorphine, a μ-agonist opioid, has recently been licensed for equine use, but butorphanol, a κ-agonist opioid, is more commonly used in horses. The effect of the 2 opioids has not previously been compared in a large clinical study. Objectives: To compare post operative analgesia and physiological variables in horses undergoing elective surgery following premedication with either buprenorphine or butorphanol in a conventional clinical setting. Study design: Mu...

  9. Transdermal Buprenorphine Relieves Neuropathic Pain: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial in Diabetic Peripheral Neuropathic Pain.

    Science.gov (United States)

    Simpson, Richard W; Wlodarczyk, John H

    2016-09-01

    To evaluate the efficacy and safety of transdermal buprenorphine in patients with diabetic peripheral neuropathic pain (DPNP). This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial enrolled patients with type 1 or type 2 diabetes and stable glycemic control who had been experiencing moderate to severe DPNP for at least 6 months on maximal tolerated conventional therapy. Patients were randomly assigned to receive buprenorphine (5 μg/h) or placebo patches. The dose was titrated to effect to a maximum of 40 μg/h. Paracetamol was available as rescue analgesia. The severity of pain and other symptoms of DPNP were assessed daily in a patient diary and at clinic visits. One hundred eight-six patients were enrolled, with 93 randomized to either buprenorphine or placebo. A high proportion of patients did not complete the study (buprenorphine 37 of 93, placebo 24 of 93). The main reason for premature withdrawal in the buprenorphine group was adverse events commonly due to untreated nausea and/or vomiting. Among the per-protocol population, more patients in the buprenorphine group (86.3%) experienced a 30% reduction in average versus baseline pain at week 12 than those in the placebo group (56.6%, P buprenorphine group within the intention-to-treat analysis of the same end point (51.7% vs. 41.3%, P = 0.175). Transdermal buprenorphine, when tolerated, is an effective therapy for DPNP and provides another option to manage this challenging painful condition. Nausea and constipation need to be managed proactively to optimize treatment outcomes. © 2016 by the American Diabetes Association.

  10. Pronociceptive and Antinociceptive Effects of Buprenorphine in the Spinal Cord Dorsal Horn Cover a Dose Range of Four Orders of Magnitude

    Science.gov (United States)

    Gerhold, Katharina J.; Drdla-Schutting, Ruth; Honsek, Silke D.; Forsthuber, Liesbeth

    2015-01-01

    Due to its distinct pharmacological profile and lower incidence of adverse events compared with other opioids, buprenorphine is considered a safe option for pain and substitution therapy. However, despite its wide clinical use, little is known about the synaptic effects of buprenorphine in nociceptive pathways. Here, we demonstrate dose-dependent, bimodal effects of buprenorphine on transmission at C-fiber synapses in rat spinal cord dorsal horn in vivo. At an analgesically active dose of 1500 μg·kg−1, buprenorphine reduced the strength of spinal C-fiber synapses. This depression required activation of spinal opioid receptors, putatively μ1-opioid receptors, as indicated by its sensitivity to spinal naloxone and to the selective μ1-opioid receptor antagonist naloxonazine. In contrast, a 15,000-fold lower dose of buprenorphine (0.1 μg·kg−1), which caused thermal and mechanical hyperalgesia in behaving animals, induced an enhancement of transmission at spinal C-fiber synapses. The ultra-low-dose buprenorphine-induced synaptic facilitation was mediated by supraspinal naloxonazine-insensitive, but CTOP-sensitive μ-opioid receptors, descending serotonergic pathways, and activation of spinal glial cells. Selective inhibition of spinal 5-hydroxytryptamine-2 receptors (5-HT2Rs), putatively located on spinal astrocytes, abolished both the induction of synaptic facilitation and the hyperalgesia elicited by ultra-low-dose buprenorphine. Our study revealed that buprenorphine mediates its modulatory effects on transmission at spinal C-fiber synapses by dose dependently acting on distinct μ-opioid receptor subtypes located at different levels of the neuraxis. PMID:26134641

  11. Patient Perspectives on Buprenorphine/Naloxone: A Qualitative Study of Retention During the Starting Treatment with Agonist Replacement Therapies (START) Study

    Science.gov (United States)

    Teruya, Cheryl; Schwartz, Robert P.; Mitchell, Shannon Gwin; Hasson, Albert L.; Thomas, Christie; Buoncristiani, Samantha H.; Hser, Yih-Ing; Wiest, Katharina; Cohen, Allan J.; Glick, Naomi; Jacobs, Petra; McLaughlin, Paul; Ling, Walter

    2014-01-01

    This study examines the barriers and facilitators of retention among patients receiving buprenorphine/naloxone at eight community-based opioid treatment programs across the United States. Participants (n=105) were recruited up to three-and-a-half years after having participated in a randomized clinical trial comparing the effect of buprenorphine/naloxone and methadone on liver function. Semi-structured interviews were conducted with 67 patients provided with buprenorphine/naloxone who had terminated early and 38 patients who had completed at least 24 weeks of the trial. Qualitative data were analyzed using the constant comparison method. Barriers to buprenorphine/naloxone retention that emerged included factors associated with: (1) the design of the clinical trial, (2) negative medication or treatment experience, and (3) personal circumstances. The facilitators comprised: (1) positive experience with the medication, (2) personal determination and commitment to complete, and (3) staff encouragement and support. The themes drawn from interviews highlight the importance of considering patients’ prior experience with buprenorphine/naloxone and methadone, medication preference, personal circumstances, and motivation to abstain from illicit use or misuse of opioids, as these may influence retention. Ongoing education of patients and staff regarding buprenorphine/naloxone, especially in comparison to methadone, and support from staff and peers are essential. PMID:25364994

  12. Patient perspectives on buprenorphine/naloxone: a qualitative study of retention during the starting treatment with agonist replacement therapies (START) study.

    Science.gov (United States)

    Teruya, Cheryl; Schwartz, Robert P; Mitchell, Shannon Gwin; Hasson, Albert L; Thomas, Christie; Buoncristiani, Samantha H; Hser, Yih-Ing; Wiest, Katharina; Cohen, Allan J; Glick, Naomi; Jacobs, Petra; McLaughlin, Paul; Ling, Walter

    2014-01-01

    This study examines the barriers and facilitators of retention among patients receiving buprenorphine/naloxone at eight community-based opioid treatment programs across the United States. Participants (n = 105) were recruited up to three and a half years after having participated in a randomized clinical trial comparing the effect of buprenorphine/naloxone and methadone on liver function. Semi-structured interviews were conducted with 67 patients provided with buprenorphine/naloxone who had terminated early and 38 patients who had completed at least 24 weeks of the trial. Qualitative data were analyzed using the constant comparison method. Barriers to buprenorphine/naloxone retention that emerged included factors associated with: (1) the design of the clinical trial; (2) negative medication or treatment experience; and (3) personal circumstances. The facilitators comprised: (1) positive experience with the medication; (2) personal determination and commitment to complete; and (3) staff encouragement and support. The themes drawn from interviews highlight the importance of considering patients' prior experience with buprenorphine/naloxone and methadone, medication preference, personal circumstances, and motivation to abstain from illicit use or misuse of opioids, as these may influence retention. Ongoing education of patients and staff regarding buprenorphine/naloxone, especially in comparison to methadone, and support from staff and peers are essential.

  13. Effects of two doses of buprenorphine four or six hours apart on nociceptive thresholds, pain and sedation in dogs after castration.

    Science.gov (United States)

    Slingsby, L S; Taylor, P M; Waterman-Pearson, A E

    2006-11-18

    Twenty-eight dogs were randomly allocated into two groups. They were premedicated with either 10 or 20 microg/kg buprenorphine and 0.05 mg/kg acepromazine administered intramuscularly, and then anaesthetised with intravenous thiopentone to effect and maintained with isoflurane in 100 per cent oxygen. The dogs underwent routine castration, and a second dose of 10 microg/kg buprenorphine was administered four hours after the first or 20 microg/kg six hours after the first dose. Levels of pain and sedation were scored on a visual analogue scale and in terms of the dogs' requirement for rescue analgesia, and mechanical nociceptive thresholds were measured at the hock and wound at premedication and one, two, three, four, five, six, seven, 10 and 21 to 22 hours later. Pain scores were low in both groups, with a trend for lower scores in the high dose group; administration of the second dose of buprenorphine further decreased the pain scores. Buprenorphine produced good preoperative sedation and the level of sedation decreased over time after surgery. Administration of the second high dose of buprenorphine did not increase the level of sedation. Both doses of buprenorphine prevented hyperalgesia at the wound and hock postoperatively. Three dogs given the low dose and one dog given the high dose required rescue analgesia with carprofen.

  14. A Retrospective Cohort Study of Obstetric Outcomes in Opioid-Dependent Women Treated with Implant Naltrexone, Oral Methadone or Sublingual Buprenorphine, and Non-Dependent Controls.

    Science.gov (United States)

    Kelty, Erin; Hulse, Gary

    2017-07-01

    Opioid pharmacotherapies play an important role in the treatment of opioid-dependent women; however, very little is known about the safety of naltrexone in pregnant patients. This study examined the obstetric health of opioid-dependent women who were treated with implant naltrexone during pregnancy, and compared them with women treated with methadone and/or buprenorphine and a cohort of non-opioid-dependent controls. Women treated with implant naltrexone, oral methadone or sublingual buprenorphine between 2001 and 2010, along with a cohort of age-matched controls, were linked with records from midwives, hospital and emergency departments (EDs) and the death registry to identify pregnancy and health events that occurred during pregnancy and in the post-partum period. Overall rates of pregnancy loss (requiring hospital or ED attendance) were significantly elevated in naltrexone-treated women compared with buprenorphine-treated women (p = 0.018) and controls (p buprenorphine groups, and neither were overall complications during pregnancy and labour. Overall rates of complications during pregnancy were significantly higher in the naltrexone-treated women than in the controls. Opioid-dependent women treated with naltrexone implant had higher rates of birth than the other three groups (methadone- or buprenorphine-treated women, or age-matched controls). Overall rates of complications during pregnancy were elevated in naltrexone-treated women when compared with the control group, but were generally not significantly different to rates in methadone- or buprenorphine-treated women.

  15. Management of opioid addiction with buprenorphine: French history and current management

    Directory of Open Access Journals (Sweden)

    Poloméni P

    2014-03-01

    Full Text Available Pierre Poloméni,1 Raymund Schwan2,3 1Department of Addictology, Paris Seine Saint Denis University Hospital, AP-HP, Site René Muret Sevran, France; 2Care Center for the Treatment and Prevention of Addictions (CSAPA, Nancy University Hospital, 3General Psychiatric Division for the Greater Nancy Urban Community, Psychotherapeutic Center of Nancy, Laxou, France Abstract: The way in which opioid addiction is managed in France is unique, as it is based on the prescription of buprenorphine by general practitioners and is dispensed by retail pharmacies. This policy has had a direct, positive impact on the number of deaths caused by heroin overdose, which was reduced by four-fifths between 1994 and 2002. In addition, certain associated comorbidities, such as infection with the human immunodeficiency virus, have also been reduced; the incidence of acquired immune deficiency syndrome in intravenous drug users fell from 25% in the mid-1990s to 6% in 2010. Since the implementation of this French model of opioid management, major scientific progress has been made, leading to a better understanding of the pathophysiologic mechanisms of addiction and of the management modalities required for its treatment. However, despite notable advances in scientific knowledge and in the implementation of devices, opioid addiction remains a major public health care issue in France, with 275,000–360,000 "problem drug users" being reported in 2011. The situation is still particularly worrying due to psychoactive substance use and misuse of opioid substitution treatments. Since 2003, there has been a persistent increase in the number of deaths and comorbidities related to opioid addiction, principally hepatitis C virus infection, which affects up to 40% of intravenous drug users. In France, the direct involvement of general practitioners in the management of opioid addiction is indisputable. Nevertheless, management could be optimized through better understanding of the

  16. Buprenorphine with bupivacaine for intraoral nerve blocks to provide postoperative analgesia in outpatients after minor oral surgery.

    Science.gov (United States)

    Modi, Mancy; Rastogi, Sanjay; Kumar, Ashish

    2009-12-01

    The demonstration that opioid receptors exist in the peripheral nervous system offers the possibility of providing postoperative analgesia in the ambulatory surgical patient. Over the previous decade, many investigators have studied this approach and have compared the efficacy of various opioids added to the local anesthetic near the brachial plexus; and it appears from several of these studies that buprenorphine provides the longest duration of analgesia, the most important parameter of postoperative analgesia in outpatients. One of these studies indicated that the agonist-antagonist, buprenorphine, added to bupivacaine provided a longer period of postoperative analgesia than the traditional opiates, but none of the studies was performed in patients undergoing minor oral surgery to check the efficacy of buprenorphine to provide postoperative analgesia in dental patients. The present study was undertaken to ascertain the efficacy of buprenorphine in providing prolonged postoperative analgesia when added to 0.5% bupivacaine with epinephrine 1:200,000. Fifty healthy, consenting adult patients scheduled for upper extremity surgery were enrolled in the study. Patients were assigned randomly to 1 of 2 equal groups based on the agents used for the blocks. Patients in group I received 40 mL of a local anesthetic alone, and those in group II received the same local anesthetic plus buprenorphine 0.3 mg. The study was kept double-blind by having one dentist prepare the solutions, a second dentist perform the blocks, and a third dentist monitor the anesthesia and analgesia thereafter, up to and including the time of the first request for an analgesic medication. The data were reported as means +/- standard errors of the mean, and differences between groups were determined using t test. A P value less than .01 was considered statistically significant. The mean duration of postoperative pain relief after injection of the local anesthetic alone was 8.34 +/- 0.11 hours compared

  17. Development, Implementation, and Evaluation of a Pilot Parenting Educational Intervention in a Pregnancy Buprenorphine Clinic.

    Science.gov (United States)

    Giles, Averie C; Ren, Dianxu; Founds, Sandra

    2016-01-01

    We developed a pilot evidence-based prenatal educational intervention to increase knowledge of neonatal abstinence syndrome (NAS) and early parenting skills for women with opiate dependency who enrolled in a pregnancy buprenorphine clinic. We developed, implemented, and tested modules regarding expectations during newborn hospitalization for observation or treatment of NAS and regarding evidence-based parenting skills in response to NAS behaviors. Testing evaluated baseline knowledge of early parenting skills with newborns at risk for NAS and change from baseline after the educational intervention. No statistically significant difference in composite knowledge scores was observed. A brief survey completed by the participants postpartum affirmed the perception of women that the educational intervention effectively prepared them for the early postpartum period while their newborns were hospitalized. © 2016 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

  18. Facile synthesis of ( sup 11 C)buprenorphine for positron emission tomographic studies of opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Lever, J.R.; Dannals, R.F.; Wagner, H.N. Jr. (Johns Hopkins Univ., Baltimore, MD (USA). School of Hygiene and Public Health Johns Hopkins Univ., Baltimore, MD (USA). Dept. of Radiology); Mazza, S.M. (Johns Hopkins Univ., Baltimore, MD (USA). School of Hygiene and Public Health); Ravert, H.T.; Wilson, A.A. (Johns Hopkins Univ., Baltimore, MD (USA). Dept. of Radiology)

    1990-01-01

    We have developed a simple and rapid method for the production of buprenorphine (BPN), a potent opioid partial agonist, labelled with carbon-11 at the 6-methoxy position. The procedure uses a precursor synthesized in high yield (89%) from BPN in two steps and employs ({sup 11}C)iodomethane as the radiolabelling reagent. ({sup 11}C)BPN of 97% radiochemical purity can be prepared in high specific activity (41 GBq/{mu}mol; 1120 mCi/{mu}mol) in a radiochemical yield of 10% at end-of-synthesis (not decay corrected). The ({sup 11}C)BPN is available for use in studies of cerebral opioid receptors by positron emission tomography within 24 min from end-of-bombardment, including radiosynthesis, purification, formulation for i.v. injection and determination of specific activity. (author).

  19. Budgetary impact analysis of buprenorphine-naloxone combination (Suboxone®) in Spain

    Science.gov (United States)

    2012-01-01

    Background Opioid addiction is a worldwide problem. Agonist opioid treatment (AOT) is the most widespread and frequent pharmacotherapeutic approach. Methadone has been the most widely used AOT, but buprenorphine, a partial μ-opiod agonist and a κ-opiod antagonist, is fast gaining acceptance. The objective was to assess the budgetary impact in Spain of the introduction of buprenorphine-naloxone (B/N) combination. Methods A budgetary impact model was developed to estimate healthcare costs of the addition of B/N combination to the therapeutic arsenal for treating opioid dependent patients, during a 3-year period under the National Health System perspective. Inputs for the model were obtained from the specialized scientific literature. Detailed information concerning resource consumption (drug cost, logistics, dispensing, medical, psychiatry and pharmacy supervision, counselling and laboratory test) was obtained from a local expert panel. Costs are expressed in euros (€, 2010). Results The number of patients estimated to be prescribed B/N combination was 2,334; 2,993 and 3,589 in the first, second and third year respectively. Total budget is €85,766,129; €79,855,471 and €79,137,502 in the first, second and third year for the scenario without B/N combination. With B/N combination the total budget would be €86,589,210; €80,398,259 and €79,708,964 in the first, second and third year of the analyses. Incremental cost/patient comparing the addition of the B/N combination to the scenario only with methadone is €10.58; €6.98 and €7.34 in the first, second and third year respectively. Conclusion Addition of B/N combination would imply a maximum incremental yearly cost of €10.58 per patient compared to scenario only with methadone and would provide additional benefits. PMID:22828157

  20. Efficacy of transdermal buprenorphine patch on post-operative pain relief after elective spinal instrumentation surgery

    Directory of Open Access Journals (Sweden)

    Saikat Niyogi

    2017-01-01

    Full Text Available Background and Aims: Transdermal buprenorphine patch (TDB is increasingly used for chronic pain management because of non-invasive dosing, longer duration of action and minimal side effects. However its role in acute post-operative pain management for spinal instrumentation surgery is not well established. The aim of this study was to evaluate the analgesic efficacy of buprenorphine patch for postoperative pain relief in patients undergoing spinal instrumentation surgery. Methods: In this randomised, placebo-controlled, double-blinded, prospective study, 70 adult patients undergoing elective spinal instrumentation surgery were randomly allocated into two groups-TDB Group (buprenorphinepatch and TDP Group (placebo patch. Time to first rescue analgesic requirement was the primary outcome. All patients also were monitored for total rescue analgesic requirement, drug-related adverse effect and haemodynamic status till 48 h after surgery. Statistical analysis was carried out using student independent t-test if normally distributed or with Mann–Whitney U-test if otherwise. Results: Time to first post-operative rescue analgesic (tramadol requirement was much delayed in TDB Group than TDP Group (708.0 ± 6.98 min vs 54 ± 0.68 min, P < 0.001 and the total tramadol requirement was higher in TDB Group (490.60 ± 63.09 averagevs. 162.93 ± 63.91 mg, P < 0.001. Intra-and post-operative haemodynamic status was also stable in TDB Group without any adverse event. Conclusion: A TDB patch (10 μg/hour applied 24 hours before surgery can be used as a postoperative analgesic for lumber fixation surgery without any drug-related adverse effect.

  1. Effects of tramadol and buprenorphine on select immunologic factors in a cecal ligation and puncture model.

    Science.gov (United States)

    Hugunin, Kelly M S; Fry, Christopher; Shuster, Katherine; Nemzek, Jean A

    2010-09-01

    Sepsis research relies on animal models. The models that most closely resemble clinical disease, such as cecal ligation and puncture, require surgery. After surgery, analgesics may not be included in experimental protocols because of concern over effects on inflammatory responses. This often generates animal welfare controversies within institutions; however, there are no scientific studies directly addressing the effects of analgesics on surgical models of sepsis. The purpose of this study was to characterize the effects of opioids on key parameters used in sepsis research.Female ICR mice were divided into four treatment groups (Ringer's lactate solution, high- or low-dose tramadol,buprenorphine) for 3-week mortality studies (n = 12 per treatment). Experimental groups were then repeated, and mice were killed at 12, 24, and 48 h postsurgery for cell counts, differentials, and cytokine levels in blood, peritoneum, and airways. Mortality studies demonstrated no significant differences between controls and any treatment group. However,significant differences were noted between buprenorphine and high-dose tramadol, revealing more and later deaths with tramadol. For comparison of immune parameters, Mann-Whitney U or Student t test was performed, emphasizing comparisons between treatment and control. Although several results were significant, comparisons between control and any treatment group yielded no differences that remained consistently apparent during the observation period. Again,differences were observed between the treatments. The results suggest that judicious and limited use of some analgesics may not dramatically affect the outcome of similarly conducted cecal ligation and puncture studies when compared with those not using analgesics. However, when different analgesics are used, comparisons between studies may be complicated.

  2. [Trend in buprenorphine and methadone shopping behavior in France from 2004 to 2014].

    Science.gov (United States)

    Kernisant, Mélanie; Delorme, Jessica; Kabore, Jean-Luc; Brousse, Georges; Laporte, Catherine; Zenut, Marie; Chenaf, Chouki; Authier, Nicolas

    2016-12-01

    The opioid maintenance treatments (OMT) are widely misused and diverted in many countries. Doctor shopping represented the main way to obtain high quantities of opioids in abuse/diversion. The aim of this study was to assess the trends in the prevalence of doctor shopping for high dosage buprenorphine (HDB) and methadone (MTD) from 2004 to 2014 by using the French Health Insurance claims. This was a cross-sectional study of patients treated by OMT (High Dosage Buprenorphine or Methadone) between 2004 and 2014 from a representative sample of the French Health Insurance claims. Doctor shopping was defined as at least 1 day of overlapping prescriptions, written by at least 2 different prescribers and filled in at least 3 different pharmacies. HDB patients were more likely men (77.9 % in 2014) with a mean age ranged from 33.4±7.6 years in 2004 to 39.5±9.3 years in 2014, Pshopping for HDB decreased from 2004 to 2014 (12.6 % versus 3.9 %, Pshopping for MTD was very low during the period study (0.2 % to 0.5 %). Overall, the prevalence of doctor shopping was higher for HDB than for MTD whatever the year (Pshopping for HDB decreased significantly during the last decade while doctor shopping for MTD remained nearly inexistent even if it could be underestimated because of dispensations in specialized centers and in hospitals not comprised in the insurance claims. The low rates of doctor shopping reported in these last years could result from the guidelines for good practices in OMT use made in 2004 and the adjustments of ANSM (French National Agency for Medicines and Health Products Safety) for HDB best use made in 2011. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Buprenorphine provides better anaesthetic conditions than butorphanol for field castration in ponies: results of a randomised clinical trial.

    Science.gov (United States)

    Rigotti, C; De Vries, A; Taylor, P M

    A prospective, randomised, blinded, clinical trial in 47 ponies compared butorphanol and buprenorphine administered intravenously with detomidine prior to castration under anaesthesia. Detomidine 12 μg/kg intravenously was followed by butorphanol 25 μg/kg (BUT) or buprenorphine 5 μg/kg (BUP) before induction of anaesthesia with intravenous ketamine and diazepam. Quality of sedation, induction and recovery from anaesthesia, response to tactile stimulation, and surgical conditions were scored. If anaesthesia was inadequate 'rescue' was given with intravenous ketamine (maximum three doses) followed by intravenous thiopental and detomidine. Time from induction to first rescue, total ketamine dose and number of rescues were recorded. Postoperative locomotor activity was scored and abnormal behaviour noted. Simple descriptive scales were used for all scoring. Data were analysed using two-way analysis of variance, t tests, Mann-Whitney or Fisher's exact tests as appropriate; Pbuprenorphine appeared to provide better intraoperative analgesia. British Veterinary Association.

  4. Morphine and buprenorphine do not alter leukocyte cytokine production capacity, early apoptosis, or neutrophil phagocytic function in healthy dogs.

    Science.gov (United States)

    Monibi, Farrah A; Dodam, John R; Axiak-Bechtel, Sandra M; Amorim, Juliana; Zhang, Yan; Tsuruta, Kaoru; Mann, F A; DeClue, Amy E

    2015-04-01

    Opioids have immunomodulatory properties in many species, but there is little information pertaining to these properties in dogs. Our objective was to compare the in vivo effects of morphine, buprenorphine, and control solution on innate immune system function and apoptosis in healthy dogs. Six adult dogs received a 24-hour infusion of morphine, buprenorphine, or control solution (saline) in a randomized, controlled, crossover block design. Leukocyte apoptosis, phagocytosis, and oxidative burst were evaluated using flow cytometry. Lipopolysaccharide, lipoteichoic acid, and peptidoglycan-stimulated leukocyte production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 were determined using canine specific multiplex assays. No significant treatment effects were detected among groups. These data suggest that healthy dogs could be less sensitive to the immunomodulatory effects of acute opioid administration compared with other species. Larger investigations in healthy and immunologically challenged dogs are recommended prior to application of these results in clinical patients. Copyright © 2015. Published by Elsevier Ltd.

  5. Determination of an optimal dose of medetomidine-ketamine-buprenorphine for anaesthesia in the Cape ground squirrel (Xerus inauris

    Directory of Open Access Journals (Sweden)

    K. E. Joubert

    2011-04-01

    Full Text Available The optimal dose of medetomidine-ketamine-buprenorphine was determined in 25 Cape ground squirrels (Xerus inauris undergoing surgical implantation of a temperature logger into the abdominal cavity. At the end of anaesthesia, the squirrels were given atipamezole intramuscularly to reverse the effects of medetomidine. The mean dose of medetomidine was 67.6±9.2 μg/kg, ketamine 13.6±1.9 mg/kg and buprenorphine 0.5±0.06 μg/kg. Induction time was 3.1 ± 1.4 min. This produced surgical anaesthesia for 21± 4.2 min. Atipamezole 232±92 μg/kg produced a rapid recovery. Squirrels were sternally recumbent in 3.5 ± 2.2 min.

  6. Preparation of (/sup 11/C)buprenorphine - a potential radioligand for the study of the opiate receptor system in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Luthra, S.K.; Pike, V.W.; Brady, F.; Horlock, P.L.; Prenant, C.; Crouzel, C.

    1987-01-01

    A method is described for the preparation of (/sup 11/C)buprenorphine in high specific activity, based on the reaction of N-(de-cyclopropylmethyl)buprenorphine with ''no carrier added'' (1-/sup 11/C)cyclopropanecarbonyl chloride followed by reduction with lithium aluminium hydride. The (1-/sup 11/C)cyclopropanecarbonyl chloride is itself prepared from cyclotron-produced (/sup 11/C)carbon dioxide. The overall preparation time is 57 min from the end of radionuclide production, and the radiochemical yield is ca 20%, (decay-corrected from (/sup 11/C)-carbon dioxide). (/sup 11/C)Buprenophine has potential as a radio-ligand for the study of the opiate receptor system in vivo by means of position emission tomography.

  7. Simultaneous quantification of buprenorphine, naloxone and phase I and II metabolites in plasma and breastmilk by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Swortwood, Madeleine J; Scheidweiler, Karl B; Barnes, Allan J; Jansson, Lauren M; Huestis, Marilyn A

    2016-05-13

    Opioid abuse during pregnancy is associated with fetal growth restriction, placental abruption, preterm labor, fetal death, and Neonatal Abstinence Syndrome. Current guidelines for medication-assisted opioid addiction treatment during pregnancy are methadone or buprenorphine monotherapy. Buprenorphine/naloxone combination therapy (Suboxone(®)) has not been thoroughly evaluated during pregnancy and insufficient naloxone safety data exist. While methadone- and buprenorphine-treated mothers are encouraged to breastfeed, no studies to date investigated naloxone concentrations during breastfeeding following Suboxone administration. For this reason, we developed and fully validated a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of buprenorphine, buprenorphine-glucuronide, norbuprenorphine, norbuprenorphine-glucuronide, naloxone, naloxone-glucuronide and naloxone-N-oxide in 100μL human plasma and breastmilk in a single injection following protein precipitation and solid-phase extraction. Lowest limits of quantification were 0.1-2μg/L with 20-100μg/L upper limits of linearity. Bias and imprecision were <±16%. Matrix effects ranged from -57.9 to 11.2 and -84.6 to 29.3% in plasma and breastmilk, respectively. All analytes were stable (within ±20% change from baseline) under all tested conditions (24h room temperature, 72h at 4°C, 3 freeze/thaw cycles at -20°C, and in the autosampler for 72h at 4°C). For proof of concept, buprenorphine and its metabolites were successfully quantified in authentic positive maternal and infant plasma and paired breastmilk specimens. This comprehensive, highly sensitive and specific method detects multiple buprenorphine markers in a small specimen volume. Published by Elsevier B.V.

  8. Safety and clinical effectiveness of a compounded sustained-release formulation of buprenorphine for postoperative analgesia in New Zealand White rabbits.

    Science.gov (United States)

    DiVincenti, Louis; Meirelles, Luiz A D; Westcott, Robin A

    2016-04-01

    To determine the clinical effectiveness and safety of a compounded sustained-release formulation of buprenorphine, compared with effects of regular buprenorphine, for postoperative analgesia in rabbits. Blinded randomized controlled clinical trial. 24 purpose-bred adult male New Zealand White rabbits. Rabbits received titanium implants in each tibia as part of another study. Immediately prior to surgery, each rabbit received regular buprenorphine hydrochloride (0.02 mg/kg [0.009 mg/lb], SC, q 12 h for 3 days) or 1 dose of a compounded sustained-release formulation of buprenorphine (0.12 mg/kg [0.055 mg/lb], SC) followed by an equal volume of saline (0.9% NaCl) solution (SC, q 12 h for 3 days) after surgery. For 7 days after surgery, rabbits were evaluated for signs of pain by means of rabbit grimace and activity scoring and for adverse effects. No significant differences were identified between treatment groups in grimace and activity scores at any point. No major adverse effects were detected for either drug. However, 3 rabbits that received regular buprenorphine had pain scores suggestive of moderate to severe pain by the time dose administration was due (ie, within the 12-hour administration interval). No clinically important differences were detected in intraoperative anesthetic or postoperative recovery variables. Sustained-release buprenorphine administered SC at 0.12 mg/kg was at least as effective as regular buprenorphine in providing analgesia for rabbits following orthopedic surgery without any major adverse effects. This sustained-release formulation represents an important alternative for rabbit analgesia with potential to improve rabbit welfare over existing analgesic standards.

  9. Methadone vs. buprenorphine/naloxone during early opioid substitution treatment: a naturalistic comparison of cognitive performance relative to healthy controls

    OpenAIRE

    Rapeli, Pekka; Fabritius, Carola; Alho, Hannu; Salaspuro, Mikko; Wahlbeck, Kristian; Kalska, Hely

    2007-01-01

    Background Both methadone- and buprenorphine-treated opioid-dependent patients frequently show cognitive deficits in attention, working memory, and verbal memory. However, no study has compared these patient groups with each other during early opioid substitution treatment (OST). Therefore, we investigated attention, working memory, and verbal memory of opioid-dependent patients within six weeks after the introduction of OST in a naturalistic setting and compared to those of healthy controls....

  10. Preference for brand-name buprenorphine is related to severity of addiction among outpatients in opioid maintenance treatment.

    Science.gov (United States)

    Binder, Philippe; Messaadi, Nassir; Perault-Pochat, Marie-Christine; Gagey, Stéphanie; Brabant, Yann; Ingrand, Pierre

    2016-01-01

    As a form of opioid maintenance treatment, high-dose buprenorphine is increasingly being used in the United States. On the French market since 1996, it is the most commonly prescribed and frequently employed opioid maintenance treatment. For unknown reasons, the brand-name form is used far more often than the generic form (76-24%). The objective was to show that the patients' levels of addiction were differentiated according to the form of buprenorphine currently being used and to their previous experience of a different form. An observational study in 9 sites throughout France used self-assessment questionnaires filled out in retail pharmacies by all patients to whom their prescribed buprenorphine treatment was being delivered. The 151 canvassed pharmacies solicited 879 patients, of whom 724 completed the questionnaires. Participants were statistically similar to non-participants. The patients using the brand-name form subsequent to experience with the generic form exhibited a more elevated addiction severity index and a higher dosage than brand-name form users with no experience of a different form. Compared to generic users, their doses were higher, their was addiction more severe, and their alcohol consumption was more excessive; they were also more likely to make daily use of psychotropic substances. However, the level of misuse or illicit consumption was similar between these groups. Preferring the brand-name buprenorphine form to the generic form is associated with a higher level of severe addiction, a more frequent need for daily psychotropics, and excessive drinking; but the study was unable to show a causal link.

  11. Opioid addiction and abuse in primary care practice: a comparison of methadone and buprenorphine as treatment options.

    Science.gov (United States)

    Bonhomme, Jean; Shim, Ruth S; Gooden, Richard; Tyus, Dawn; Rust, George

    2012-01-01

    Opioid abuse and addiction have increased in frequency in the United States over the past 20 years. In 2009, an estimated 5.3 million persons used opioid medications nonmedically within the past month, 200000 used heroin, and approximately 9.6% of African Americans used an illicit drug. Racial and ethnic minorities experience disparities in availability and access to mental health care, including substance use disorders. Primary care practitioners are often called upon to differentiate between appropriate, medically indicated opioid use in pain management vs inappropriate abuse or addiction. Racial and ethnic minority populations tend to favor primary care treatment settings over specialty mental health settings. Recent therapeutic advances allow patients requiring specialized treatment for opioid abuse and addiction to be managed in primary care settings. The Drug Addiction Treatment Act of 2000 enables qualified physicians with readily available short-term training to treat opioid-dependent patients with buprenorphine in an office-based setting, potentially making primary care physicians active partners in the diagnosis and treatment of opioid use disorders. Methadone and buprenorphine are effective opioid replacement agents for maintenance and/or detoxification of opioid-addicted individuals. However, restrictive federal regulations and stigmatization of opioid addiction and treatment have limited the availability of methadone. The opioid partial agonist-antagonist buprenorphine/naloxone combination has proven an effective alternative. This article reviews the literature on differences between buprenorphine and methadone regarding availability, efficacy, safety, side-effects, and dosing, identifying resources for enhancing the effectiveness of medication-assisted recovery through coordination with behavioral/psychological counseling, embedded in the context of recovery-oriented systems of care.

  12. Comparison of premedication with buprenorphine or methadone with meloxicam for postoperative analgesia in dogs undergoing orthopaedic surgery.

    Science.gov (United States)

    Hunt, J R; Attenburrow, P M; Slingsby, L S; Murrell, J C

    2013-08-01

    To determine whether methadone, administered before orthopaedic surgery, results in improved postoperative analgesia compared to buprenorphine. Thirty-eight dogs undergoing orthopaedic surgeries (the majority being tibial tuberosity advancement or elbow arthrotomy) were premedicated with 0 · 03 mg/kg acepromazine and either 20 µg/kg buprenorphine or 0 · 5 mg/kg methadone, intramuscularly, allocated randomly. Anaesthesia was induced with propofol intravenously to effect and maintained with isoflurane in oxygen. 0 · 2 mg/kg meloxicam was administered at anaesthetic induction. Sedation was assessed by means of a dynamic interactive visual analogue and simple descriptive scales and pain by dynamic interactive visual analogue and the short form Glasgow composite pain scales, by a single observer blinded to treatment group at intervals for 8 hours following premedication. Sedation scores were higher than baseline in both groups following premedication until the end of the assessment period (P = 0 · 0001), with no differences between groups. Pain scores were lower overall in dogs premedicated with methadone (dynamic interactive visual analogue scale P = 0 · 048; short form Glasgow composite pain scale P = 0 · 0045), and these dogs required less additional analgesia (42%, compared to 79% premedicated with buprenorphine, P = 0 · 045). At the doses investigated, methadone produced superior analgesia to buprenorphine for 8 hours postoperatively in dogs undergoing orthopaedic surgery. © 2013 British Small Animal Veterinary Association.

  13. Comparison of the analgesic efficacy of oral ABT-116 administration with that of transmucosal buprenorphine administration in dogs.

    Science.gov (United States)

    Niyom, Sirirat; Mama, Khursheed R; De Rezende, Marlis L

    2012-04-01

    To evaluate the analgesic efficacy of ABT-116, a transient receptor potential cation channel vanilloid subfamily V member 1 antagonist, and compare it with that of buprenorphine by measurement of mechanical and thermal nociceptive thresholds in dogs. Six 7- to 8-month-old dogs (3 males and 3 females). In a crossover study design, all dogs received ABT-116 (30 mg/kg, PO) and buprenorphine (0.03 mg/kg, orotransmucosally), with each treatment separated by 1 week. Physiologic variables were recorded prior to and 1, 6, and 24 hours after drug administration. Thermal (thoracic) and mechanical (dorsolateral aspect of the radius [proximal] and dorsopalmar aspect of the forefoot [distal]) nociceptive thresholds were assessed prior to (baseline) and 15 minutes and 1, 2, 4, 6, 12, 18, and 24 hours after treatment. Buprenorphine administration resulted in higher overall thermal and proximal mechanical nociceptive thresholds, compared with ABT-116. Distal mechanical nociceptive thresholds after treatment were higher than baseline values for both treatments, but the magnitude of change was greater for buprenorphine at 1 hour after administration. Whereas HR and RR sporadically differed from baseline values after ABT-116 administration, rectal temperature increased from a baseline value of 39 ± 0.2°C (mean ± SD) to a peak of 40.6 ± 0.2°C at 6 hours. In dogs without inflammation or nerve injury, PO administration of ABT-116 did not consistently result in an increase in nociceptive thresholds. However, clinically relevant increases in rectal temperature were identified after ABT-116 administration.

  14. Primary tumour growth in an orthotopic osteosarcoma mouse model is not influenced by analgesic treatment with buprenorphine and meloxicam.

    Science.gov (United States)

    Husmann, K; Arlt, M J E; Jirkof, P; Arras, M; Born, W; Fuchs, B

    2015-10-01

    Little is known about the treatment of bone pain in animal models of bone cancer. In the present study, the orthotopic 143-B human osteosarcoma xenotransplantation model was used to address the following questions: (1) Can repetitive analgesic treatment extend the experimental period by prolonging the time to reach humane endpoints and (2) Does repetitive analgesic treatment affect bone tumour development and metastasis? The analgesics, buprenorphine and meloxicam, were either applied individually or in combination at 12 h intervals as soon as the animals began to avoid using the tumour cell injected leg. While control mice treated with NaCl showed continuous body weight loss, the major criterion previously for terminating the experiments, animals treated with analgesic substances did not. The control mice had to be sacrificed 26 days after tumour cell injection, whereas the groups of animals with the different pain treatments were euthanized after an additional eight days. Importantly, primary intratibial tumour growth was not affected in any of the experimental groups by any of the pain treatment procedures. Between days 26 and 34 after tumour cell injection an increase of about 100% of the number of lung metastases was found for the groups treated with buprenorphine alone or together with meloxicam, but not for the group treated with meloxicam alone. In summary, the results indicated that both buprenorphine and meloxicam are suitable analgesics for prolonging the experimental periods in an experimental intratibial osteosarcoma mouse model. © The Author(s) 2015.

  15. Assessment of the sedative effects of buprenorphine administered with 10 μg/kg detomidine in horses.

    Science.gov (United States)

    Love, E J; Taylor, P M; Murrell, J; Whay, H R; Waterman-Pearson, A E

    2011-04-09

    The aim of this randomised, observer-blinded, crossover study was to compare the effects of six treatments, administered intravenously to six horses: saline and saline (S/S); detomidine and saline (D/S); detomidine and 5 µg/kg buprenorphine (D/B5); detomidine and 7.5 µg/kg buprenorphine (D/B7.5); detomidine and 10 µg/kg buprenorphine (D/B10); and detomidine and 25 µg/kg butorphanol (D/BUT). The detomidine dose was 10 µg/kg for all treatments in which it was included. Sedation was subjectively assessed and recorded on a visual analogue scale. Peak sedation, duration of sedation and the area under the curve (AUC) for sedation scores were investigated using a univariate general linear model with post-hoc Tukey tests (P<0.05). Peak sedation and duration of sedation were statistically significantly different between treatments (P<0.001). No sedation was apparent after administration of S/S. The AUC was significantly different between treatments (P=0.010), with S/S being significantly different from D/S, D/BUT, D/B5 and D/B7.5, but not D/B10 (P=0.051).

  16. Assessment of Carprofen and Buprenorphine on Recovery of Mice after Surgical Removal of the Mammary Fat Pad

    Science.gov (United States)

    Adamson, Trinka W; Kendall, Lon V; Goss, Sherri; Grayson, Kevin; Touma, Chadi; Palme, Rupert; Chen, Jane Q; Borowsky, Alexander D

    2010-01-01

    The purpose of this study was to determine the level of pain elicited by mammary fat pad removal surgery and the effects of postoperative analgesics on recovery. Female FVB mice were anesthetized, and mammary fat pad removal was performed. After surgery, mice received carprofen, buprenorphine, a combination of carprofen and buprenorphine, or saline treatment. Additional mice received anesthesia but no surgery or treatment. Food and water intake, body weight, wheel running activity, and a visual assessment score were recorded daily for 4 d after surgery and compared with presurgical findings. Corticosterone metabolites in fecal samples were analyzed at 12 and 24 h postsurgically and compared with baseline values. All surgical groups had significantly decreased food intake at 24 h, with a return to baseline by 48 h. The combination treatment resulted in a significantly decreased water intake and body weight at 24 h. All surgical groups had significantly decreased wheel running activity at 24 h only. The visual assessment scores indicated mild pain for all surgical groups, with the buprenorphine treated mice showing the highest pain index scores, as compared with nonsurgical controls. Fecal corticosterone metabolite levels did not differ significantly between any of the groups or across time. The parameters used in this study did not indicate that administration of these analgesic regimens improved recovery as compared with that of saline-treated mice. Care should be taken when using visual assessment scores to evaluate pain in mice, given that analgesics may have side effects that inadvertently elevate the score. PMID:20858363

  17. Correlates of Nine-Month Retention following Interim Buprenorphine-Naloxone Treatment in Opioid Dependence: A Pilot Study

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    A. Håkansson

    2016-01-01

    Full Text Available Interim medication-only treatment has been suggested for the initiation of opioid maintenance treatment (OMT in opioid-dependent subjects, but this rarely has been studied using buprenorphine instead of methadone. Following a pilot trial assessing interim buprenorphine-naloxone treatment in order to facilitate transfer into OMT, we here aimed to study retention, and potential correlates of retention, in full-scale treatment. Thirty-six patients successfully referred from a waiting list through an interim treatment phase were followed for nine months in OMT. Baseline characteristics, as well as urine analyses during the interim phase and during full-scale OMT, were studied as potential correlates of retention. The nine-month retention in OMT was 83 percent (n=30. While interim-phase urine samples positive for benzodiazepines did not significantly predict dropout from full-scale OMT (p=0.09, urine samples positive for benzodiazepines within full-scale OMT were significantly associated with dropout (p<0.01, in contrast to other substances and baseline characteristics. Retention remained high through nine months in this pilot study sample of patients referred through buprenorphine-naloxone interim treatment, but use of benzodiazepines is problematic, and the present data suggest that it may be associated with treatment dropout.

  18. Simultaneous determination of buprenorphine, norbuprenorphine and naloxone in human plasma by liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Liu, Yongzhen; Li, Xiaohua; Xu, Allan; Nasser, Azmi F; Heidbreder, Christian

    2016-02-20

    A simple, sensitive and rapid liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for simultaneous quantification of naloxone, buprenorphine and its metabolite norbuprenorphine in human plasma. Human plasma samples were extracted using a single step liquid-liquid extraction, and then separated on an Imtakt Unison UK-C18 column (2.1×50mm, 3μm) using alkaline mobile phases with gradient elution. All of the analytes were detected in positive ion mode using multiple reaction monitoring (MRM). The method was validated and the specificity, linearity, lower limit of quantitation, precision, accuracy, recoveries and stability were determined. The linear range was 20-10000pg/mL for buprenorphine and norbuprenorphine; and 1-500pg/mL for naloxone. The correlation coefficient (R(2)) values for all three analytes were ≥0.995. The precision and accuracy for intra-day and inter-day were 63% and matrix effects were tracked by the deuterated internal standards (IS) with the IS-normalized matrix factor ranging from 0.96 to 1.33 for all three analytes. The validated method was successfully applied in a clinical pharmacokinetic study with low dose administration of sublingual buprenorphine and naloxone. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. In patients undergoing fast track total knee arthroplasty, addition of buprenorphine to a femoral nerve block has no clinical advantage A prospective, double-blinded, randomized, placebo controlled trial

    NARCIS (Netherlands)

    van Beek, Rienk; Zonneveldt, Harry J.; van der Ploeg, Tjeerd; Steens, Jeroen; Lirk, Phillip; Hollmann, Marcus W.

    2017-01-01

    Background: Several adjuvants have been proposed to prolong the effect of peripheral nerve blocks, one of which is buprenorphine. In this randomized double blinded placebo controlled trial we studied whether the addition of buprenorphine to a femoral nerve block prolongs analgesia in patients

  20. Comparison of prescriber evaluations and patient-directed self-reports in office-based practice for buprenorphine treatment of opiate-dependent individuals in France, 2002

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    Estelle Lavie

    2008-11-01

    Full Text Available Estelle Lavie1, Mélina Fatséas1, Jean-Pierre Daulouède1,2, Cécile Denis1, Jacques Dubernet1, Laurent Cattan3, Marc Auriacombe11Laboratoire de psychiatrie/EA4139, INSERM IFR-99 and Faculté de médecine Victor Pachon, University Victor Segalen Bordeaux 2, Bordeaux, France; 2Bizia, Centre de soins d’addictologie, Centre Hospitalier de la Côte Basque, Bayonne, France; 3Centre médical, Noisy-le-sec, FranceAbstract: The objective of this cross-sectional evaluation study was to compare data generated through prescriber assessments, and data generated from independent direct contact with opiate-dependent patients in office-based practice to evaluate buprenorphine treatment for modality of buprenorphine absorption, benzodiazepine use, and depressive symptoms. A group of buprenorphine office-based practice prescribers was selected to participate in this study. They were asked to screen for inclusion all their patients coming for a visit from February to August 2002. Once included by their prescribing physician, patients were given a series of self-administered questionnaires to be returned directly to the research staff, independently of their prescriber. Each prescriber was given a questionnaire to complete based on their knowledge and interview of the patient. Items assessed were history of current treatment, current substance use, buprenorphine treatment related behavior (daily frequency of intake, route of administration, benzodiazepine use and existence of a major depressive episode. Prescribers and patients’ questionnaires were compared. Concordance of both assessments was assessed by kappa statistics. The sensitivity and specificity as well as the positive and negative predictive values of prescriber collected information were compared to that of their patients’. There was an overall good correlation between both data sources on the procedures for buprenorphine use especially for intravenous use of buprenorphine. There were important

  1. Long-term safety and analgesic efficacy of buprenorphine buccal film in patients with moderate-to-severe chronic pain requiring around-the-clock opioids

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    Hale M

    2017-01-01

    Full Text Available Martin Hale,1 Veronica Urdaneta,2 M Todd Kirby,3 Qinfang Xiang,4 Richard Rauck5 1Gold Coast Research, LLC, Plantation, FL, USA; 2Pharmacovigilance and Risk Management, 3Clinical Development, 4Biometrics, Endo Pharmaceuticals Inc., Malvern, PA, USA; 5Carolinas Pain Institute, Wake Forest Baptist Health, Winston Salem, NC, USA Background: This open-label, single-arm study was conducted to evaluate the long-term safety and efficacy of a novel buprenorphine formulation, buprenorphine buccal film, in the treatment of moderate-to-severe chronic pain requiring around-the-clock opioids.Methods: The primary purpose of this study was to evaluate the long-term safety and tolerability of buprenorphine buccal film. Five hundred and six patients who completed previous studies with buprenorphine buccal film (n=445; rollover patients or were recruited de novo for this study (n=61 were enrolled in this study. All patients underwent a dose titration period of ≤6 weeks, during which doses of buprenorphine buccal film were adjusted to a maximum 900 µg every 12 hours, depending on tolerability and the need for rescue medication. An optimal dose was defined as the dose that the patient found satisfactory for both pain relief and tolerability, without the need for rescue medication or with ≤2 tablets of rescue medication per day. Once the optimal dose was reached, treatment was continued for ≤48 weeks. Pain intensity was measured throughout the study using a 0–10 numerical rating scale.Results: Of 435 patients achieving an optimal dose of buprenorphine buccal film who commenced long-term treatment, 158 (36.3% completed 48 weeks of treatment. Treatment-related adverse events occurred in 116 patients (22.9% during the titration phase and 61 patients (14.0% during the long-term treatment phase, and adverse events leading to discontinuation of treatment occurred in 14 (2.8% and 14 (3.2% patients, respectively. The most common adverse events were those typically

  2. The Effect of a Payer-Mandated Decrease in Buprenorphine Dose on Aberrant Drug Tests and Treatment Retention Among Patients with Opioid Dependence.

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    Accurso, Anthony J; Rastegar, Darius A

    2016-02-01

    The optimal dose for office-based buprenorphine therapy is not known. This study reports on the effect of a change in payer policy, in which the insurer of a subset of patients in an office-based practice imposed a maximum sublingual buprenorphine dose of 16 mg/day, thereby forcing those patients on higher daily doses to decrease their dose. This situation created conditions for a natural experiment, in which treatment outcomes for patients experiencing this dose decrease could be compared to patients with other insurance who were not challenged with a dose decrease. Subjects were 297 patients with opioid use disorder in a primary care practice who were prescribed buprenorphine continuously for at least 3 months. Medical records were retrospectively reviewed for urine drug test results and treatment retention. Rates of aberrant urine drug tests were calculated in the period before the dose decrease and compared to rate after it with patients serving as their own controls. Comparison groups were formed from patients with the same insurance on buprenorphine doses of 16 mg/day or lower, patients with different insurance on 16 mg/day or lower, and patients with different insurance on greater than 16 mg/day. Rates of aberrant drug tests and treatment retention of patients on 16 mg/day or less of buprenorphine were compared to that of patients on higher daily doses. The rate of aberrant urine drug tests among patients who experienced a dose decrease rose from 27.5% to 34.2% (p=0.043). No comparison group showed any significant change in aberrant drug test rates. Moreover, all groups who were prescribed buprenorphine doses greater than 16 mg/day displayed lower rates of aberrant urine drug tests than groups prescribed lower doses. Retention in treatment was also highest among those prescribed greater than 16 mg/day (100% vs. 86.8%, 90.1%, and 84.4% p=0.010). An imposed buprenorphine dose decrease was associated with an increase in aberrant drug tests. Patients in a

  3. Trends in Receipt of Buprenorphine and Naltrexone for Opioid Use Disorder Among Adolescents and Young Adults, 2001-2014.

    Science.gov (United States)

    Hadland, Scott E; Wharam, J Frank; Schuster, Mark A; Zhang, Fang; Samet, Jeffrey H; Larochelle, Marc R

    2017-08-01

    Opioid use disorder (OUD) frequently begins in adolescence and young adulthood. Intervening early with pharmacotherapy is recommended by major professional organizations. No prior national studies have examined the extent to which adolescents and young adults (collectively termed youth) with OUD receive pharmacotherapy. To identify time trends and disparities in receipt of buprenorphine and naltrexone among youth with OUD in the United States. A retrospective cohort study was conducted using deidentified data from a national commercial insurance database. Enrollment and complete health insurance claims of 9.7 million youth, aged 13 to 25 years were analyzed, identifying individuals who received a diagnosis of OUD between January 1, 2001, and June 30, 2014, with final follow-up date December 31, 2014. Analysis was conducted from April 25 to December 31, 2016. Time trends were identified and multivariable logistic regression was used to determine sociodemographic factors associated with medication receipt. Sex, age, race/ethnicity, neighborhood education and poverty levels, geographic region, census region, and year of diagnosis. Dispensing of a medication (buprenorphine or naltrexone) within 6 months of first receiving an OUD diagnosis. Among 20 822 youth diagnosed with OUD (0.2% of the 9.7 million sample), 13 698 (65.8%) were male and 17 119 (82.2%) were non-Hispanic white. Mean (SD) age was 21.0 (2.5) years at the first observed diagnosis. The diagnosis rate of OUD increased nearly 6-fold from 2001 to 2014 (from 0.26 per 100 000 person-years to 1.51 per 100 000 person-years). Overall, 5580 (26.8%) youth were dispensed a medication within 6 months of diagnosis, with 4976 (89.2%) of medication-treated youth receiving buprenorphine and 604 (10.8%) receiving naltrexone. Medication receipt increased more than 10-fold, from 3.0% in 2002 (when buprenorphine was introduced) to 31.8% in 2009, but declined in subsequent years (27.5% in 2014). In multivariable

  4. A multicentre, prospective, randomised, blinded clinical trial to compare some perioperative effects of buprenorphine or butorphanol premedication before equine elective general anaesthesia and surgery.

    Science.gov (United States)

    Taylor, P M; Hoare, H R; de Vries, A; Love, E J; Coumbe, K M; White, K L; Murrell, J C

    2016-07-01

    Buprenorphine, a μ-agonist opioid, has recently been licensed for equine use, but butorphanol, a κ-agonist opioid, is more commonly used in horses. The effect of the 2 opioids has not previously been compared in a large clinical study. To compare post operative analgesia and physiological variables in horses undergoing elective surgery following premedication with either buprenorphine or butorphanol in a conventional clinical setting. Multicentre, prospective, randomised, blinded clinical investigation. Eighty-nine healthy horses admitted for elective surgery to one of 6 UK equine veterinary clinics were premedicated with acepromazine, a nonsteroidal anti-inflammatory drug, and romifidine followed by intravenous (i.v.) buprenorphine or butorphanol. Anaesthesia was induced with diazepam/ketamine and maintained with isoflurane in oxygen. A range of surgical procedures were performed and supplementary anaesthetic agents given as required. Physiological variables were monitored during anaesthesia and pain, ataxia, sedation and vital function were assessed post operatively. Data were analysed using t-tests, ANOVA, Mann-Whitney U-test and Chi-squared test as appropriate and Pbuprenorphine than after butorphanol. Horses experienced less post operative pain after buprenorphine than after butorphanol premedication. Compared with butorphanol, buprenorphine did not cause any different effects on vital function. © 2015 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of British Equine Veterinary Association.

  5. Pilot evaluation of a novel unilateral onychectomy model and efficacy of an extended release buprenorphine product.

    Science.gov (United States)

    Enomoto, Masataka; Kigin, Patricia D; Bledsoe, David; Slone, Robyn; Hash, Jonathan; Smith, Charles E; Lascelles, B Duncan X

    2017-01-24

    Non-steroidal anti-inflammatory drugs (NSAIDs), transdermal fentanyl patches, and transmucosal buprenorphine are probably the most commonly used options for providing post-operative analgesia in the early at-home period. However, these require daily administration or are associated with abuse concerns. One of the significant unmet needs in veterinary surgery and pain management is for longer acting opioids for cats to effectively bridge the gap between the in-hospital and at-home recovery periods. A proof of concept study of an extended release formulation of buprenorphine HCL (ER-Bup) was conducted using objective kinetic measures and a unilateral onychectomy model. Using a blinded, randomized, two period crossover design, four cats were allocated to control (saline) or ER-Bup (0.6 mg/kg, subcutaneously [SC]) treatment groups. All animals underwent a unilateral forelimb onychectomy per period with a washout/recovery period in between. Observational pain scores and kinetic data (using a pressure sensitive walkway [PSW]) were collected prior to (baseline) and at intervals for 72 h following surgery. Symmetry indices were derived for kinetic variables (peak vertical force [PVF]; vertical impulse [VI]) of each forelimb for landing following a jump and for walking. A rescue analgesic protocol was in place. Effect of surgery and treatment were evaluated using a mixed model statistical approach. No cats required rescue analgesics based on subjective pain score. ER-Bup had a positive influence on subjective pain scores during the 72 h postsurgery (p = 0.0473). PVF and VI of the operated limb were significantly decreased for both landing (p < 0.0001 and p < 0.0001) and walking (p < 0.0001 and p < 0.0001 respectively) compared to control. ER-Bup resulted in significantly decreased asymmetry in limb use during landing (PVF, p < 0.0001; VI, p < 0.0001) and walking (PVF, p = 0.0002, VI, p < 0.0001). The novel use of data collected

  6. Transdermal buprenorphine and fentanyl patches in cancer pain: a network systematic review

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    Ahn JS

    2017-08-01

    Full Text Available Jin Seok Ahn,1 Johnson Lin,2 Setsuro Ogawa,3 Chen Yuan,4 Tony O’Brien,5,6 Brian HC Le,7 Andrea M Bothwell,8 Hanlim Moon,9 Yacine Hadjiat,9 Abhijith Ganapathi9 1Division of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea; 2Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China; 3Department of Anesthesiology, Nihon University School of Medicine, Tokyo, Japan; 4Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5Marymount University Hospital and Hospice, 6Cork University Hospital, College of Medicine and Health, University College Cork, Cork, Ireland; 7Department of Palliative Care, Royal Melbourne Hospital, Parkville, VIC, Australia; 8In Vivo Communications (Asia, 9Mundipharma Pte Ltd, Singapore, Singapore Abstract: Treatment of cancer pain is generally based on the three-step World Health Organization (WHO pain relief ladder, which utilizes a sequential approach with drugs of increasing potency. Goals of pain management include optimization of analgesia, optimization of activities of daily living, minimization of adverse effects, and avoidance of aberrant drug taking. In addition, it is recommended that analgesic regimens are individualized and simplified to help ensure patient compliance and should provide the least invasive, easiest, and safest route of opioid administration to ensure adequate analgesia. Buprenorphine and fentanyl are two opioids available for the relief of moderate-to-severe cancer pain. Available clinical data regarding the transdermal (TD formulations of these opioids and the extent to which they fulfill the recommendations mentioned earlier are systematically reviewed, with the aim of providing additional information for oncologists and pain specialists regarding their comparative use. Due to lack of

  7. Utilizing buprenorphine-naloxone to treat illicit and prescription-opioid dependence.

    Science.gov (United States)

    Mauger, Sofie; Fraser, Ronald; Gill, Kathryn

    2014-01-01

    To review current evidence on buprenorphine-naloxone (bup/nx) for the treatment of opioid-use disorders, with a focus on strategies for clinical management and office-based patient care. Medline and the Cochrane Database of Systematic Reviews were searched. Consensus reports, guidelines published, and other authoritative sources were also included in this review. Apart from expert guidelines, data included in this review constitute level 1 evidence. Bup/nx is a partial μ-opioid agonist combined with the opioid antagonist naloxone in a 4:1 ratio. It has a lower abuse potential, carries less stigma, and allows for more flexibility than methadone. Bup/nx is indicated for both inpatient and ambulatory medically assisted withdrawal (acute detoxification) and long-term substitution treatment (maintenance) of patients who have a mild-to-moderate physical dependence. A stepwise long-term substitution treatment with regular monitoring and follow-up assessment is usually preferred, as it has better outcomes in reducing illicit opioid use, minimizing concomitant risks such as human immunodeficiency virus and hepatitis C transmission, retaining patients in treatment and improving global functioning. Bup/nx is safe and effective for opioid detoxification and substitution treatment. Its unique pharmaceutical properties make it particularly suitable for office-based maintenance treatment of opioid-use disorder.

  8. In patients undergoing fast track total knee arthroplasty, addition of buprenorphine to a femoral nerve block has no clinical advantage: A prospective, double-blinded, randomized, placebo controlled trial.

    Science.gov (United States)

    van Beek, Rienk; Zonneveldt, Harry J; van der Ploeg, Tjeerd; Steens, Jeroen; Lirk, Phillip; Hollmann, Marcus W

    2017-07-01

    Several adjuvants have been proposed to prolong the effect of peripheral nerve blocks, one of which is buprenorphine. In this randomized double blinded placebo controlled trial we studied whether the addition of buprenorphine to a femoral nerve block prolongs analgesia in patients undergoing total knee arthroplasty in a fast track surgery protocol. The treatment group (B) was given an ultrasound-guided femoral nerve block with ropivacaine 0.2% and 0.3mg buprenorphine. We choose to use 2 control groups. Group R was given a femoral nerve block with ropivacaine 0.2% only. Group S also received 0.3 mg buprenorphine subcutaneously. Only patients with a successful block were enrolled in the study. We found no difference in our primary outcome parameter of time to first rescue analgesic. We found lower opioid use and better sleep quality the first postoperative night in patients receiving buprenorphine perineurally or subcutaneously. Buprenorphine did not lead to any significant change in pain or mobilization. We found a high overall incidence of nausea and vomiting. In patients undergoing total knee arthroplasty, in the setting of a fast track surgery protocol, the addition of buprenorphine to a femoral nerve block did not prolong analgesia.

  9. Long-term administration of high doses of transdermal buprenorphine in cancer patients with severe neuropathic pain

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    Leppert W

    2015-12-01

    Full Text Available Wojciech Leppert, Grzegorz Kowalski Chair and Department of Palliative Medicine, Poznan University of Medical Sciences, Poznan, Poland Background: Buprenorphine is often administered by the transdermal route (transdermal buprenorphine [TB] in cancer patients with severe neuropathic pain. However, high doses of TB of 140 µg/h are rarely used.Patients and methods: Three cancer patients with severe neuropathic Numeric Rating Scale (NRS pain scores of 8–10 who were successfully treated with high doses of TB up to 140 µg/h along with other opioids and adjuvant analgesics.Results: TB was administered for a long period of follow-up (9 months to 4 years, including 34–261 days of treatment with the dose of 140 µg/h, which allowed achievement of satisfactory analgesia (NRS 3–5 and good treatment tolerance. In all three patients, TB dose was gradually titrated from 35 to 140 µg/h, and all patients used morphine at least for some time for breakthrough and background pain management along with adjuvant analgesics. Two patients continued the treatment with TB until the end of life, and one patient is still receiving the treatment.Conclusion: TB at doses of up to 140 µg/h in cancer patients with severe neuropathic pain seems to be effective and safe in combination with other opioids and with adjuvant analgesics, and may significantly improve patients’ quality of life. Clinical studies may explore higher than maximal 140 µg/h TB doses recommended by a manufacturer, and also in combination with other opioids and adjuvant analgesics. Keywords: adverse effects, analgesia, cancer, neuropathic pain, transdermal buprenorphine, treatment

  10. A statistical experimental design approach to evaluate the influence of various penetration enhancers on transdermal drug delivery of buprenorphine.

    Science.gov (United States)

    Taghizadeh, S Mojtaba; Moghimi-Ardakani, Ali; Mohamadnia, Fatemeh

    2015-03-01

    A series of drug-in-adhesive transdermal drug delivery systems (patch) with different chemical penetration enhancers were designed to deliver drug through the skin as a site of application. The objective of our effort was to study the influence of various chemical penetration enhancers on skin permeation rate and adhesion properties of a transdermal drug delivery system using Box-Behnken experimental design. The response surface methodology based on a three-level, three-variable Box-Behnken design was used to evaluate the interactive effects on dependent variables including, the rate of skin permeation and adhesion properties, namely peel strength and tack value. Levulinic acid, lauryl alcohol, and Tween 80 were used as penetration enhancers (patch formulations, containing 0-8% of each chemical penetration enhancer). Buprenorphine was used as a model penetrant drug. The results showed that incorporation of 20% chemical penetration enhancer into the mixture led to maximum skin permeation flux of buprenorphine from abdominal rat skin while the adhesion properties decreased. Also that skin flux in presence of levulinic acid (1.594 μg/cm(2) h) was higher than Tween 80 (1.473 μg/cm(2) h) and lauryl alcohol (0.843 μg/cm(2) h), and in mixing these enhancers together, an additional effect was observed. Moreover, it was found that each enhancer increased the tack value, while levulinic acid and lauryl alcohol improved the peel strength but Tween 80 reduced it. These findings indicated that the best chemical skin penetration enhancer for buprenorphine patch was levulinic acid. Among the designed formulations, the one which contained 12% (wt/wt) enhancers exhibited the highest efficiency.

  11. A statistical experimental design approach to evaluate the influence of various penetration enhancers on transdermal drug delivery of buprenorphine

    Directory of Open Access Journals (Sweden)

    S.Mojtaba Taghizadeh

    2015-03-01

    Full Text Available A series of drug-in-adhesive transdermal drug delivery systems (patch with different chemical penetration enhancers were designed to deliver drug through the skin as a site of application. The objective of our effort was to study the influence of various chemical penetration enhancers on skin permeation rate and adhesion properties of a transdermal drug delivery system using Box–Behnken experimental design. The response surface methodology based on a three-level, three-variable Box–Behnken design was used to evaluate the interactive effects on dependent variables including, the rate of skin permeation and adhesion properties, namely peel strength and tack value. Levulinic acid, lauryl alcohol, and Tween 80 were used as penetration enhancers (patch formulations, containing 0–8% of each chemical penetration enhancer. Buprenorphine was used as a model penetrant drug. The results showed that incorporation of 20% chemical penetration enhancer into the mixture led to maximum skin permeation flux of buprenorphine from abdominal rat skin while the adhesion properties decreased. Also that skin flux in presence of levulinic acid (1.594 μg/cm2 h was higher than Tween 80 (1.473 μg/cm2 h and lauryl alcohol (0.843 μg/cm2 h, and in mixing these enhancers together, an additional effect was observed. Moreover, it was found that each enhancer increased the tack value, while levulinic acid and lauryl alcohol improved the peel strength but Tween 80 reduced it. These findings indicated that the best chemical skin penetration enhancer for buprenorphine patch was levulinic acid. Among the designed formulations, the one which contained 12% (wt/wt enhancers exhibited the highest efficiency.

  12. Sedative and cardiorespiratory effects of dexmedetomidine and buprenorphine administered to cats via oral transmucosal or intramuscular routes.

    Science.gov (United States)

    Santos, Luiz Cesar P; Ludders, John W; Erb, Hollis N; Basher, Karen L; Kirch, Pati; Gleed, Robin D

    2010-09-01

    To determine if buprenorphine plus dexmedetomidine administered via the oral transmucosal route produces sufficient sedation in cats so that students can insert intravenous catheters. Prospective, randomized, blinded, clinical trial. Eighty-seven shelter-owned female cats aged 4-48 months, weighing 1.1-4.9 kg. Cats were randomly allocated to two treatment groups based on route of drug administration: oral transmucosal (OTM), or intramuscular (IM). Buprenorphine (20 microg kg(-1)) plus dexmedetomidine (20 microg kg(-1)) were administered as pre-medicants via one of these two routes. Prior to and 20 minutes after drug administration, heart and respiratory rates, systolic arterial pressure, and posture were measured and recorded. Twenty minutes after drug administration the same variables plus each cat's response to clipper sound, clipping, and restraint were recorded; higher scores indicated more sedation. There were no significant differences between the two groups prior to pre-medication. Within each treatment group heart rate was significantly lower 20 minutes after treatment, but it did not differ significantly between the two groups. Twenty minutes after treatment, respiratory rate was significantly less in the OTM group, but did not differ significantly between the two groups. Systolic arterial pressure did not differ within or between the two groups at either time. Scores for posture increased significantly within both groups, and cats in the IM group had higher scores after treatment. Twenty minutes after treatment, cats in the IM group had higher scores for clipping and restraint than OTM cats. Ketamine (IM) was necessary to facilitate catheterization in 25% and 16% of cats in the OTM and IM groups, respectively, but this was not significantly different. Administration of dexmedetomidine plus buprenorphine by the OTM route is easy to perform, but produces less sedation than the IM route for IV catheterization in cats.

  13. Clinical effects of buprenorphine on open field behaviour and gait symmetry in healthy and lame weaned piglets.

    Science.gov (United States)

    Meijer, Ellen; van Nes, Arie; Back, Willem; van der Staay, Franz Josef

    2015-12-01

    Lameness in pigs decreases animal welfare and economic profit for the farmer. An important reason for impaired welfare in lame animals is pain due to lameness. No direct measurement of pain is possible in animals, and methods to indirectly detect and quantify the amount of pain an animal is experiencing are urgently needed. In this study, two methods to assess pain associated with lameness in pigs were evaluated to determine if they were sensitive enough to detect a lameness reduction as an effect of an experimental analgesic medication. Asymmetry associated with lameness was objectively quantified using pressure mat kinetic parameters: peak vertical force (PVF), load rate (LR), vertical impulse (VI) and peak vertical pressure (PVP). Locomotor activity was assessed in an open field test. A dose of 0.04 mg/kg buprenorphine, a strong analgesic, was used to treat 10 lame pigs, while eight other lame pigs, treated with physiological saline solution, served as controls. Buprenorphine decreased lameness-associated asymmetry for pressure mat LR (P = 0.002), VI (P = 0.003) and PVP (P = 0.001) and increased activity of the lame pigs in the open field (P = 0.023), while saline-treated animals did not show any changes in asymmetry and became less active in the open field (P buprenorphine when used to treat moderate to severe clinical pain in a relatively small group of affected pigs. The methods used in this study may also provide promising additional tools for future research into early pain recognition and lameness treatment in pigs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Buprenorphine for postoperative analgesia: Axillary brachial plexus block versus intramuscular administration in a placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Deepali Thakur

    2015-01-01

    Full Text Available Background and Aims: Peripheral administration of opioids has been suggested for prolongation of regional analgesia. This prospective, randomized, double-blind placebo-controlled study was undertaken to compare the effect of regional (axillary brachial plexus block [ABPB] versus intramuscular (IM buprenorphine (2 μg/kg in adults. Material and Methods: Seventy-five adults undergoing upper limb surgery received ABPB with local anaesthetic (15 ml 0.5% bupivacaine, 15 ml 2% lignocaine with adrenaline 1:200,000, 9 ml normal saline [NS]. In addition, regional group RB (n = 25 received buprenorphine 2 μg/kg in ABPB and 1 ml NS IM. Systemic Group SB (n = 25 received 1 ml NS in ABPB and buprenorphine 2 μg/kg IM. Group C (n = 25 received 1 ml NS in ABPB and IM. Onset, duration of sensory and motor block, hemodynamic parameters, sedation score, pain scores using visual analog scale, duration of postoperative analgesia, rescue analgesic (RA requirement, adverse events, and patient satisfaction were noted. Results: Demographics, onset and duration of sensory, motor block were similar. RB group had longest duration of analgesia (20.61 ± 1.33 h compared to SB (10.91 ± 0.90 h and control group (5.86 ± 0.57 h (P < 0.05 RB vs. SB/C and SB vs. C. RA requirement was highest in the control group and least in RB group (P = 0.000 RB vs. SB/C and SB vs. C. SB group had a maximum number of side effects (P = 0.041, SB vs. RB/C. Patient satisfaction was highest with group RB (P < 0.05 RB vs. SB/C, and P = 0.06 SB vs. C. Conclusion: Buprenorphine 2 μg/kg in axillary plexus block provides significantly prolonged analgesia with less RA requirement and greater patient satisfaction compared to IM administration. This is highly suggestive of action on peripheral opioid receptors.

  15. Effect of Buprenorphine Weekly Depot (CAM2038) and Hydromorphone Blockade in Individuals With Opioid Use Disorder: A Randomized Clinical Trial.

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    Walsh, Sharon L; Comer, Sandra D; Lofwall, Michelle R; Vince, Bradley; Levy-Cooperman, Naama; Kelsh, Debra; Coe, Marion A; Jones, Jermaine D; Nuzzo, Paul A; Tiberg, Fredrik; Sheldon, Behshad; Kim, Sonnie

    2017-09-01

    Buprenorphine is an efficacious, widely used treatment for opioid use disorder (OUD). Daily oral transmucosal formulations can be associated with misuse, diversion, and nonadherence; these limitations may be obviated by a sustained release formulation. To evaluate the ability of a novel, weekly, subcutaneous buprenorphine depot formulation, CAM2038, to block euphorigenic opioid effects and suppress opioid withdrawal in non-treatment-seeking individuals with OUD. This multisite, double-blind, randomized within-patient study was conducted at 3 controlled inpatient research facilities. It involved 47 adults with DSM-V moderate-to-severe OUD. The study was conducted from October 12, 2015 (first patient enrolled), to April 21, 2016 (last patient visit). A total of five 3-day test sessions evaluated the response to hydromorphone (0, 6, and 18 mg intramuscular in random order; 1 dose/session/day). After the first 3-day session (ie, qualification phase), participants were randomized to either CAM2038 weekly at 24 mg (n = 22) or 32 mg (n = 25); the assigned CAM2038 dose was given twice, 1 week apart (day 0 and 7). Four sets of sessions were conducted after randomization (days 1-3, 4-6, 8-10, and 11-13). The primary end point was maximum rating on the visual analog scale for drug liking. Secondary end points included other visual analog scale (eg, high and desire to use), opioid withdrawal scales, and physiological and pharmacokinetic outcomes. A total of 46 of 47 randomized participants (mean [SD] age, 35.5 [9] years; 76% male [n = 35]) completed the study. Both weekly CAM2038 doses produced immediate and sustained blockade of hydromorphone effects (liking maximum effect, CAM2038, 24 mg: effect size, 0.813; P buprenorphine in plasma with maximum concentration around 24 hours, with an apparent half-life of 4 to 5 days and approximately 50% accumulation of trough concentration from first to second dose (trough concentration = 0.822 and 1.23 ng/mL for weeks 1

  16. Investigation of cross-species translatability of pharmacological MRI in awake nonhuman primate - a buprenorphine challenge study.

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    Stephanie Seah

    Full Text Available BACKGROUND: Pharmacological MRI (phMRI is a neuroimaging technique where drug-induced hemodynamic responses can represent a pharmacodynamic biomarker to delineate underlying biological consequences of drug actions. In most preclinical studies, animals are anesthetized during image acquisition to minimize movement. However, it has been demonstrated anesthesia could attenuate basal neuronal activity, which can confound interpretation of drug-induced brain activation patterns. Significant efforts have been made to establish awake imaging in rodents and nonhuman primates (NHP. Whilst various platforms have been developed for imaging awake NHP, comparison and validation of phMRI data as translational biomarkers across species remain to be explored. METHODOLOGY: We have established an awake NHP imaging model that encompasses comprehensive acclimation procedures with a dedicated animal restrainer. Using a cerebral blood volume (CBV-based phMRI approach, we have determined differential responses of brain activation elicited by the systemic administration of buprenorphine (0.03 mg/kg i.v., a partial µ-opioid receptor agonist, in the same animal under awake and anesthetized conditions. Additionally, region-of-interest analyses were performed to determine regional drug-induced CBV time-course data and corresponding area-under-curve (AUC values from brain areas with high density of µ-opioid receptors. PRINCIPAL FINDINGS: In awake NHPs, group-level analyses revealed buprenorphine significantly activated brain regions including, thalamus, striatum, frontal and cingulate cortices (paired t-test, versus saline vehicle, p<0.05, n = 4. This observation is strikingly consistent with µ-opioid receptor distribution depicted by [6-O-[(11C]methyl]buprenorphine ([(11C]BPN positron emission tomography imaging study in baboons. Furthermore, our findings are consistent with previous buprenorphine phMRI studies in humans and conscious rats which collectively

  17. Recidivism with opiate addicted patients on buprenorphine substitution treatment: Case report

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    Crnić Katarina B.

    2017-01-01

    Full Text Available Introduction: Opiate dependence is a serious, chronic and recurrent psychiatric disorder, whose prevalence reach epidemic proportions. This also contributes to a significant increase in mortality, associated with overdose with opiates, as well as the rise in other health and social problems of the society. The methods and availability of treatment do not correspond to increased treatment needs, and treatment success is limited by the characteristics of the disorder, or numerous risk factors, which contribute to a high percentage of recidivism. Good clinical practice guidelines have defined treatment recommendations that include high and low-demanding programs. The personalized and integrative approaches are emphasized. Case report: The patient aged 41 years, intravenous-use opiate addict from his adolescences, with numerous psychological, health and social complications of addiction, is a participant in institutional treatment, following a court order as a measure of obligatory treatment, due to criminal offenses related to addiction. The history of the disease refers to numerous unsuccessful attempts to heal and short-term abstinence in the past, mainly in penal institutions. The patient meets all the criteria defined by the guidelines for inclusion in the buprenorphine maintenance program started in the year 2013. During the four-year treatment, the doses of the drug were adapted as needed; two heroin relapses and many in-risk situations for relapse were registered. The treatment continued with close monitoring of the patient's condition and, with appropriate psychosocial interventions, contribute to keeping the patient in treatment and preventing the development of new complications of addiction, as well an improving the quality of his life. Discussion: Pharmacological treatment of opioid dependence relies on agents belonging to groups of antagonists, agonists and partial agonists of opiate receptors. The earlier programs with abstinence as a

  18. Comparison of the analgesic properties of transdermally administered fentanyl and intramuscularly administered buprenorphine during and following experimental orthopedic surgery in sheep.

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    Ahern, Benjamin J; Soma, Lawrance R; Boston, Raymond C; Schaer, Thomas P

    2009-03-01

    To evaluate the analgesic properties of transdermally administered fentanyl and IM administered buprenorphine in sheep undergoing unilateral tibial osteotomy. 20 mature sheep. Fentanyl patches (n = 15 sheep) or placebo patches (5 sheep) were applied 12 hours before sheep underwent general anesthesia and a unilateral tibial osteotomy. Buprenorphine was administered to the placebo group every 6 hours commencing at time of induction. Signs of pain were assessed every 12 hours after surgery by 2 independent observers unaware of treatment groups. There were no differences in preoperative and intraoperative physiologic data between the 2 groups. Sheep treated with fentanyl required less preoperative administration of diazepam for sedation and had significantly lower postoperative pain scores, compared with those treated with buprenorphine. No complications associated with the antebrachium at the site of patch application were detected. Under the conditions of this study, transdermally administered fentanyl was a superior option to IM administered buprenorphine for alleviation of postoperative orthopedic pain in sheep. This information can be used to assist clinicians in the development of a rational analgesic regimen for research and clinical patients.

  19. Buprenorphine/naloxone treatment practices in Malaysia: Results of national surveys of physicians and patients.

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    Vicknasingam, B; Dazali, M N M; Singh, D; Schottenfeld, R S; Chawarski, M C

    2015-07-01

    Medication assisted treatment with buprenorphine/naloxone (Bup/Nx), including prescribing and dispensing practices of general practitioners (GPs) in Malaysia and their patients' experiences with this treatment have not been systematically examined. The current study surveyed GPs providing Bup/Nx treatment and patients receiving office-based Bup/Nx treatment in Malaysia. Two cross-sectional surveys of GPs (N=115) providing outpatient Bup/Nx maintenance treatment and of patients (N=253) currently receiving Bup/Nx treatment throughout peninsular Malaysia. Physicians prescribed Bup/Nx dosages in the range of 2-4mg daily for 70% of patients and conducted urine testing in the past month on approximately 16% of their patients. In the patient survey, 79% reported taking daily Bup/Nx doses of 2mg or less; 82% reported that no urine toxicology testing had been conducted on them in the past month, 36% had an opiate positive urine test at the time of the survey, 43% reported illicit opiate use, 15% reported injection of heroin and 22% reported injection of Bup/Nx in the past month. Low daily Bup/Nx doses, lack of behavioral monitoring or counseling, and high rates of continued drug use, including injection of drugs and medications during Bup/Nx treatment in Malaysia, indicate continuing problems with implementation and less than optimal treatment effectiveness. High cost of Bup/Nx in Malaysia may deter patients from seeking treatment and contribute to taking low Bup/Nx dosages. Improved training of physicians and establishing standards for Bup/Nx dosing, routine toxicology testing, and counseling may be needed to improve care and treatment response. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth☆

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    Warden, Diane; Subramaniam, Geetha A.; Carmody, Thomas; Woody, George E.; Minhajuddin, Abu; Poole, Sabrina A.; Potter, Jennifer; Fishman, Marc; Bogenschutz, Michael; Patkar, Ashwin; Trivedi, Madhukar H.

    2012-01-01

    Background In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment. Methods Opioid dependent adolescents and young adults (n=152), aged 15–21, were randomized to 12 weeks (BUP, n=74) or 2 weeks of detoxification (DETOX, n=78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression. Results In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition. Conclusions Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/ Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics. PMID:22626890

  1. Antinociceptive effects of sustained-release buprenorphine in a model of incisional pain in rats (Rattus norvegicus).

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    Chum, Helen H; Jampachairsri, Katechan; McKeon, Gabriel P; Yeomans, David C; Pacharinsak, Cholawat; Felt, Stephen A

    2014-03-01

    Effective management of postoperative pain is an essential component of the care and welfare of laboratory animals. A sustained-release formulation of buprenorphine (Bup-SR) has recently been introduced to the veterinary market and has been reported to provide analgesia for as long as 72 h. Using evoked mechanical and thermal hypersensitivity tests, we here evaluated the antinociceptive effects of Bup-SR in a model of incisional pain in rats. Paw withdrawal responses were obtained before and 1 through 4 d after surgery. Rats are assigned to receive Bup-SR (0.3, 1.2, or 4.5 mg/kg SC once) or buprenorphine HCl (Bup HCl, 0.05 mg/kg SC twice daily for 3 d). Responses to mechanical and thermal stimuli in the 1.2 and 4.5 Bup-SR groups did not differ from those of rats in the Bup HCl group. Thermal latency on day 3 in rats that received 0.3 mg/kg Bup-SR was significantly different from baseline, indicating that this dose effectively decreased thermal hypersensitivity for at least 48 h. Marked sedation occurred in rats in the 4.5 Bup-SR group. Our findings indicate that Bup-SR at 0.3 or 1.2 mg/kg SC is effective in minimizing hypersensitivity with minimal sedation for at least 48 h (thermal hypersensitivity) and 72 h, respectively, in the incisional pain model in rats.

  2. (R)- and (S)-methadone and buprenorphine concentration ratios in maternal and umbilical cord plasma following chronic maintenance dosing in pregnancy.

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    Gordon, Andrea L; Lopatko, Olga V; Somogyi, Andrew A; Foster, David J R; White, Jason M

    2010-12-01

    The aim of this study was to compare the transfer of buprenorphine and methadone between maternal and cord blood in women under chronic dosing conditions and to determine if differences exist in the transfer of the two methadone enantiomers. Maternal and cord blood samples were collected at delivery from women maintained on methadone (35, 25-140 mg day⁻¹) (median; range) or buprenorphine (6.00, 2-20 mg day⁻¹) during pregnancy. Plasma concentration ratios are presented as an indicator of foetal exposure relative to the mother. Methadone was quantified in all samples, with cord : maternal plasma methadone concentration ratios (n= 15 mother-infant pairs) being significantly higher (P cord (1.40; 0.95, 1.67) compared with maternal plasma (1.16; 0.81, 1.38). Half the infant buprenorphine samples were below the assay lower limit of quantification (LLOQ) (0.125 ng ml⁻¹). The latter was four-fold lower than the LLOQ for methadone (0.50 ng ml⁻¹). The cord : maternal plasma buprenorphine concentration ratio (n= 9 mother-infant pairs) was 0.35; 0.14, 0.47 and for norbuprenorphine 0.49; 0.24, 0.91. The transfer of the individual methadone enantiomers to the foetal circulation is stereoselective. Infants born to buprenorphine maintained women are not exposed to a greater proportion of the maternal dose compared with methadone and may be exposed to relatively less of the maternal dose compared with infants born to women maintained on methadone during pregnancy. © 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.

  3. The Supply of Physicians Waivered to Prescribe Buprenorphine for Opioid Use Disorders in the United States: A State-Level Analysis

    Science.gov (United States)

    Knudsen, Hannah K.

    2015-01-01

    Objective: The U.S. Food and Drug Administration’s approval of buprenorphine in 2002 expanded options for treating opioid use disorder (OUD). Physicians who intend to treat OUD patients with buprenorphine must seek a waiver to prescribe it, which may contribute to state-by-state variation in the supply of waivered physicians. Method: This study integrates data extracted from the U.S. Drug Enforcement Agency’s database of waivered physicians with state-level indicators of the macro environment, health-related resources, and treatment demand. Results: In December 2013, the average state had 8.0 waivered physicians per 100,000 residents (SD = 5.2). Large regional differences between states in the Northeast relative to states in the Midwest, South, and West were observed. The percentage of residents covered by Medicaid as well as the population-adjusted availability of opioid treatment programs and substance use disorder treatment facilities were positively associated with buprenorphine physician supply. Buprenorphine physician supply was positively correlated with states’ rates of overdose deaths, suggesting that physicians may seek the waiver in response to the magnitude of the opioid problem in their state. Conclusions: States with greater health-related resources, particularly in terms of the supply of opioid treatment programs and substance use disorder treatment programs, had more waivered physicians in 2013. The finding regarding Medicaid coverage suggests that states implementing Medicaid expansion under health reform may experience additional growth in buprenorphine physician supply. However, large regional disparities in the supply of waivered physicians may impede access to care for many Americans with OUD. PMID:26098042

  4. Addition of buprenorphine to local anesthetic in adductor canal blocks after total knee arthroplasty improves postoperative pain relief: a randomized controlled trial.

    Science.gov (United States)

    Krishnan, Sandeep H; Gilbert, Lisa A; Ghoddoussi, Farhad; Applefield, Daniel J; Kassab, Safa S; Ellis, Terry A

    2016-09-01

    For the hundreds of thousands of patients who undergo total knee arthroplasty (TKA) in the United States each year, early mobilization has been demonstrated to improve functional outcomes and reduce complications. Management of postoperative pain is a critical factor in achieving early mobilization. Recent studies have shown that the use of an adductor canal block (ACB) after TKA results in increased preservation of quadriceps muscle strength, without significant difference in postoperative pain when compared to femoral nerve block. This increased preservation of quadriceps muscle strength leads to earlier mobilization. Studies have also demonstrated a prolongation of analgesia with the addition of buprenorphine to local anesthetic for regional block placement. This study examined the effect on postoperative opioid consumption when adding buprenorphine to an ACB vs an ACB with local anesthetic alone, for postoperative analgesia after unilateral TKA. A total of 100 patients scheduled for TKA were randomized to receive postoperative ACB with local anesthetic alone or with local anesthetic and buprenorphine. The primary outcome examined was total opioid analgesic (milligrams of hydrocodone equivalent) consumption in the first 24 hours postsurgery. The secondary outcomes examined were the reported incidence of the opioid side effects nausea, vomiting, and pruritis. Postoperative opioid consumption decreased significantly in the group that received an ACB with local anesthetic and buprenorphine compared to an ACB with local anesthetic only (25.34±2.62 vs 35.84±2.86; P=.0076). Secondary outcomes showed no statistical difference between the 2 groups in terms of the incidence of nausea, vomiting, or pruritus. The addition of buprenorphine to an adductor canal block decreases postoperative opioid consumption when compared to an ACB with local anesthetic alone. This reduction in opioid consumption, without significant increase in side effects, makes this an attractive

  5. Evaluation of drug-drug interaction between daclatasvir and methadone or buprenorphine/naloxone

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    Tushar Garimella

    2014-11-01

    Full Text Available Introduction: Daclatasvir (DCV is a potent hepatitis C virus (HCV NS5A replication complex inhibitor with pangenotypic (1–6 activity in vitro. Methadone (MET and buprenorphine (BUP are opioid medications used to treat opioid addiction; patients on HCV therapy may require MET or BUP treatment. The effect of DCV on the pharmacokinetics (PK of MET or BUP/naloxone (NLX was assessed in subjects on stable MET or BUP. Materials and Methods: An open-label, two-part study assessed the effect of steady-state oral administration of DCV on the PK of MET (Part 1, P1 or BUP/NAL (Part 2, P2. Safety/tolerability and pharmacodynamics (PD, opioid withdrawal scales/overdose assessment were also assessed. Subjects (P1, N=14; P2, N=11 received daily single-dose oral MET (40–120mg or BUP/NLX (8/2–24/6mg based on their prescribed stable dose throughout, in addition to DCV (60mg QD on Days 2–9. Serial PK sampling occurred predose and postdose till 24 hours on Day 1 (MET/BUP and Day 10 (MET/BUP/DCV. Noncompartmental PK were derived. Geometric mean ratios (GMR and 90% confidence intervals (90% CI for MET/BUP/norBUP Cmax and AUCTAU were derived from linear mixed effects models. Results: Subjects were aged 19–39 years, mostly white (P1, 93%; P2, 100% and male (P1, 71%; P2, 91%. All subjects completed the study. No clinically meaningful effect was demonstrated as the GMR and 90% CIs fell within the prespecified interval (P1, 0.7–1.4; P2, 0.5–2.0: see Table 1. DCV coadministration was well-tolerated: overall, six (43% subjects had adverse events (AEs (all mild and resolved without treatment. DCV had no clinically significant effect on the PD of MET or BUP/NLX. Conclusions: Steady-state administration of DCV 60mg QD had no clinically meaningful effect on the PK of MET or BUP/NLX and was generally well-tolerated, suggesting that no dose adjustments will be required.

  6. Buprenorphine maintenance treatment retention improves nationally recommended preventive primary care screenings when integrated into urban federally qualified health centers.

    Science.gov (United States)

    Haddad, Marwan S; Zelenev, Alexei; Altice, Frederick L

    2015-02-01

    Buprenorphine maintenance therapy (BMT) expands treatment access for opioid dependence and can be integrated into primary health-care settings. Treating opioid dependence, however, should ideally improve other aspects of overall health, including preventive services. Therefore, we examined how BMT affects preventive health-care outcomes, specifically nine nationally recommended primary care quality health-care indicators (QHIs), within federally qualified health centers (FQHCs) from an observational cohort study of 266 opioid-dependent patients initiating BMT between 07/01/07 and 11/30/08 within Connecticut's largest FQHC network. Nine nationally recommended preventive QHIs were collected longitudinally from electronic health records, including screening for chronic infections, metabolic conditions, and cancer. A composite QHI score (QHI-S), based on the percentage of eligible QHIs achieved, was categorized as QHI-S ≥80% (recommended) and ≥90% (optimal). The proportion of subjects achieving a composite QHI-S ≥80 and ≥90 % was 57.1 and 28.6%, respectively. Screening was highest for hypertension (91.0%), hepatitis C (80.1%), hepatitis B (76.3%), human immunodeficiency virus (71.4%), and hyperlipidemia (72.9%) and lower for syphilis (49.3%) and cervical (58.5%), breast (44.4%), and colorectal (48.7%) cancer. Achieving QHI-S ≥80% was positively and independently associated with ≥3-month BMT retention (adjusted odds ratio (AOR) = 2.19; 95% confidence interval (CI) = 1.18-4.04) and BMT prescription by primary care providers (PCPs) rather than addiction psychiatric specialists (AOR = 3.38; 95% CI = 1.78-6.37), and negatively with being female (AOR = 0.30; 95% CI = 0.16-0.55). Within primary health-care settings, achieving greater nationally recommended health-care screenings or QHIs was associated with being able to successfully retain patients on buprenorphine longer (3 months or more) and when buprenorphine was prescribed

  7. Budgetary impact of the utilization of buprenorphine/naloxone sublingual film and tablet for Medicaid in the United States.

    Science.gov (United States)

    Asche, Carl V; Clay, Emilie; Kharitonova, Elizaveta; Zah, Vladimir; Ruby, Jane; Aballéa, Samuel

    2015-01-01

    The buprenorphine/naloxone combination for the treatment of opioid dependence is available in a film or tablet formulation. Recent retrospective studies demonstrated that treatment with the sublingual film formulation is associated with improved treatment retention and lower healthcare costs. In March 2013, generic buprenorphine/naloxone tablets were approved in the US. A budget impact model was built to compare healthcare expenditures for different market shares of sublingual film and tablet. A Markov model was developed to track a cohort of opioid dependent patients treated with sublingual film or tablet through the following treatment phases: initiation, maintenance, discontinuation, off-treatment and reinitiation. Transition probabilities and costs for each phase were estimated from the MarketScan Medicaid database for the period between 1 March 2010 and 30 June 2012. The total expenditure for the plan and expenditure per plan member per month were predicted over 5 years. Two market share scenarios were considered: 1) sublingual film is progressively replaced by generic tablet (current situation) and 2) the sublingual film holds a market share of 100%. Predicted total costs over 5 years were $6400 million when the sublingual film holds a market share of 100% (as per Scenario 2) which is lower than when sublingual film is progressively replaced by generic tablet (current situation as per Scenario 1) by $64 million. These savings were mostly driven by inpatient care ($56 million saved over 5 years), followed by emergency room care ($27 million) and pharmaceutical costs ($24 million). Costs of outpatient care attenuated the difference as they were predicted to be higher by $44 million in Scenario 2. The reduction in total cost per member per month reached $0.027 in the fifth year. Results were most sensitive to price rebates and to the probability of non-psychiatric hospitalization. While using the sublingual film formulation for more patients treated with

  8. The Severity, Frequency, and Variety of Crime in Heroin-Dependent Prisoners Enrolled in a Buprenorphine Clinical Trial

    Science.gov (United States)

    Gordon, Michael S.; Kinlock, Timothy W.; Schwartz, Robert P.; Couvillion, Kathryn A.; O’Grady, Kevin E.

    2014-01-01

    Data were obtained on four dimensions of criminal activity (frequency, variety, severity, and income) from male and female prisoners (N = 200) with preincarceration heroin dependence who participated in a randomized clinical trial of buprenorphine treatment. The article examines the above-mentioned dimensions of crime and their relationships with demographic characteristics, substance use, legitimate employment, drug treatment episodes, and psychological problems. Results largely show several important similarities to results on previous prison inmate cohorts with histories of heroin addiction, although the present sample may have more of a tendency toward violent crime than earlier cohorts of heroin-dependent offenders. This study’s findings may have implications for the design of appropriate treatment interventions for prisoners with preincarceration heroin dependence that address not only substance use but also criminal activity. PMID:25392564

  9. Sciatic and femoral nerve blockade using bupivacaine alone, or in combination with dexmedetomidine or buprenorphine in cats.

    Science.gov (United States)

    Evangelista, M C; Doodnaught, G M; Fantoni, D T; Steagall, P V M

    2017-06-17

    The aim of this study was to determine the onset and offset of antinociception after sciatic (ScN) and femoral (FN) nerve blocks. Six healthy adult cats (4.8±1.3years; 4.3±0.4 kg) were included in a randomised, crossover, blinded and controlled study. Following sedation with dexmedetomidine (25 µg/kg, intramuscular), each ScN and FN injection was performed using 0.1 ml/kg of saline (CONTROL), bupivacaine (0.46 per cent, 0.46 mg/kg; BUPI), bupivacaine and dexmedetomidine (1 µg/kg; BUPI-DEX) or bupivacaine and buprenorphine (2.5 µg/kg; BUPI-BUPRE). Atipamezole (250 µg/kg) was administered after injections. Paw withdrawal thresholds (PWT) and motor blockade were evaluated before sedation and up to 24 hours. The PWT were significantly increased at half an hour in CONTROL, from two to four hours in BUPI and BUPI-DEX when compared with baseline. Motor blockade was observed between one and three hours in treatments using bupivacaine. Ability to walk was significantly impaired in BUPI at half an hour to two hours, BUPI-DEX at one to two hours and BUPI-BUPRE at two hours. Antinociception was observed in BUPI between one and eight hours, and in BUPI-DEX and BUPI-BUPRE between one and four hours. This study could not demonstrate a benefit of administering bupivacaine with dexmedetomidine or buprenorphine in cats. Results in BUPI-DEX may have been biased by the administration of atipamezole. British Veterinary Association.

  10. Opioid receptor imaging and displacement studies with [6-O-[{sup 11}C]methyl]buprenorphine in baboon brain

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    Galynker, Igor; Schlyer, David J.; Dewey, Stephen L.; Fowler, Joanna S.; Logan, Jean; Gatley, S. John; MacGregor, Robert R.; Ferrieri, Richard A.; Holland, M. J.; Brodie, Jonathan; Simon, Eric; Wolf, Alfred P

    1996-04-01

    Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O-[{sup 11}C]methyl]buprenorphine ([{sup 11}C]BPN) to measure the regional distribution in baboon brain, the test-retest stability of repeated studies in the same animal, the displacement of the labeled drug by naloxone in vivo, and the tissue distribution in mice. The regional distribution of radioactivity in baboon brain determined with PET was striatum > thalamus > cingulate gyrus > frontal cortex > parietal cortex > occipital cortex > cerebellum. This distribution corresponded to opiate receptor density and to previously published data (37). The tracer uptake in adult female baboons showed no significant variation in serial scans in the same baboon with no intervention in the same scanning session. HPLC analysis of baboon plasma showed the presence of labeled metabolites with 92% {+-} 2.2% and 43% {+-} 14.4% of the intact tracer remaining at 5 and 30 min, respectively. Naloxone, an opiate receptor antagonist, administered 30-40 min after tracer injection at a dose of 1.0 mg/kg i.v., reduced [{sup 11}C]BPN binding in thalamus, striatum, cingulate gyrus, and frontal cortex to values 0.25 to 0.60 of that with no intervention. There were minimal (< 15%) effects on cerebellum. Naloxone treatment significantly reduced the slope of the Patlak plot in receptor-containing regions. These results demonstrate that [{sup 11}C]BPN can be displaced by naloxone in vivo, and they affirm the feasibility of using this tracer and displacement methodology for short-term kinetics studies with PET. Mouse tissue distribution data were used to estimate the radiation dosimetry to humans. The critical organ was the small intestine, with a radiation dose estimate to humans of 117 nrad/mCi.

  11. Incidence of high dosage buprenorphine and methadone shopping behavior in a retrospective cohort of opioid-maintained patients in France.

    Science.gov (United States)

    Delorme, Jessica; Chenaf, Chouki; Kabore, Jean-Luc; Pereira, Bruno; Mulliez, Aurélien; Tremey, Aurore; Brousse, Georges; Zenut, Marie; Laporte, Catherine; Authier, Nicolas

    2016-05-01

    Opioid Substitution Treatment (OST) misuse and diversion have significantly increased worldwide. Obtaining OST prescriptions from multiple prescribers, known as doctor shopping, is a way in which opioids may be diverted. The aim of this study was to assess the incidence of OST (high dosage buprenorphine (HDB) and methadone (MTD)) shopping behavior and identify associated risk factors, and its impact on mortality. A retrospective cohort of patients treated by OST between April 1, 2004 and December 31, 2012 from a sample of the French Health Insurance database was established. Doctor shopping was defined as ≥1 day of overlapping prescriptions written by ≥2 different prescribers and filled in ≥3 different pharmacies. A total of 2043 patients were enrolled, 1450HDB and 593 MTD. The one-year incidence of shopping behavior was 8.4% (95% CI: 7.0-10.1) in HDB group and 0% in MTD group, compared to 0.2% (95% CI: 0.1-0.2) for diuretics. On multivariate analysis, factors associated with HDB shopping behavior were: male gender HR: 1.74 (95% CI: 1.20-2.54); low-income status HR: 2.95 (95% CI: 2.07-4.44); mental health disorders HR: 1.43 (95% CI: 1.06-1.94); concurrent hypnotics use HR: 1.90 (95% CI: 1.39-2.61); concurrent use of weak opioids HR: 1.48 (95% CI: 1.09-1.99) and morphine HR: 1.69 (95% CI: 1.02-2.80). HDB shoppers had a higher, yet non-significant risk of death (HR: 1.56 (95% CI: 0.64-3.81)) than non HDB shoppers. Shopping behavior was only found in high dosage buprenorphine patients and concerned almost one out ten patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Investigation of cross-species translatability of pharmacological MRI in awake nonhuman primate - a buprenorphine challenge study.

    Science.gov (United States)

    Seah, Stephanie; Asad, Abu Bakar Ali; Baumgartner, Richard; Feng, Dai; Williams, Donald S; Manigbas, Elaine; Beaver, John D; Reese, Torsten; Henry, Brian; Evelhoch, Jeffrey L; Chin, Chih-Liang

    2014-01-01

    Pharmacological MRI (phMRI) is a neuroimaging technique where drug-induced hemodynamic responses can represent a pharmacodynamic biomarker to delineate underlying biological consequences of drug actions. In most preclinical studies, animals are anesthetized during image acquisition to minimize movement. However, it has been demonstrated anesthesia could attenuate basal neuronal activity, which can confound interpretation of drug-induced brain activation patterns. Significant efforts have been made to establish awake imaging in rodents and nonhuman primates (NHP). Whilst various platforms have been developed for imaging awake NHP, comparison and validation of phMRI data as translational biomarkers across species remain to be explored. We have established an awake NHP imaging model that encompasses comprehensive acclimation procedures with a dedicated animal restrainer. Using a cerebral blood volume (CBV)-based phMRI approach, we have determined differential responses of brain activation elicited by the systemic administration of buprenorphine (0.03 mg/kg i.v.), a partial µ-opioid receptor agonist, in the same animal under awake and anesthetized conditions. Additionally, region-of-interest analyses were performed to determine regional drug-induced CBV time-course data and corresponding area-under-curve (AUC) values from brain areas with high density of µ-opioid receptors. In awake NHPs, group-level analyses revealed buprenorphine significantly activated brain regions including, thalamus, striatum, frontal and cingulate cortices (paired t-test, versus saline vehicle, ptranslatability of awake imaging. Conversely, no significant change in activated brain regions was found in the same animals imaged under the anesthetized condition. Our data highlight the utility and importance of awake NHP imaging as a translational imaging biomarker for drug research.

  13. Morphine- and buprenorphine-induced analgesia and antihyperalgesia in a human inflammatory pain model: a double-blind, randomized, placebo-controlled, five-arm crossover study

    Directory of Open Access Journals (Sweden)

    Ravn P

    2013-01-01

    Full Text Available Pernille Ravn,1 Erik L Secher,2 Ulrik Skram,3 Trine Therkildsen,1 Lona L Christrup,1 Mads U Werner41Department of Drug Design and Pharmacology, University of Copenhagen, 2Department of Anesthesiology, Juliane Marie Center, Rigshospitalet, Copenhagen University Hospitals, 3Department of Intensive Care, Gentofte Hospital, Copenhagen University Hospitals, 4Multidisciplinary Pain Center, Neuroscience Center, Rigshospitalet, Copenhagen University Hospitals, Copenhagen, DenmarkPurpose: Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than µ-opioid receptor agonists. The primary outcome of this study was therefore to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending pain modulation.Subjects and methods: Twenty-eight healthy subjects were included. The study was a double-blind, randomized, placebo-controlled, five-arm crossover study with a multimodal (electrical, mechanical, and thermal stimuli testing technique. After baseline assessments, intravenous infusions of morphine (10/20 mg, buprenorphine (0.3/0.6 mg, or placebo (normal saline were administered over a 210-minute period, during which a cold pressor test, heat injury (47°C, 7 minutes, 12.5 cm2, and the first postburn assessment were done. After completion of the drug infusions, two additional postburn assessments were done. The subjects were monitored during each 8-hour session by an anesthesiologist.Results: For nearly all tested variables, significant dose-dependent analgesic effects were demonstrated. The median antihyperalgesia/analgesia ratio (secondary hyperalgesia

  14. A Retrospective Cohort Study of Birth Outcomes in Neonates Exposed to Naltrexone in Utero: A Comparison with Methadone-, Buprenorphine- and Non-opioid-Exposed Neonates.

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    Kelty, Erin; Hulse, Gary

    2017-07-01

    Naltrexone may provide a suitable alternative to methadone and buprenorphine in the treatment of pregnant opioid-dependent women; however, little is known about its effects on neonatal morbidity and mortality. The aim was to evaluate the health of neonates exposed to naltrexone in utero, and compare it with outcomes in neonates exposed to methadone or buprenorphine and a non-exposed control group. Sequential cohorts of Western Australian (WA) opioid-dependent women treated with implant naltrexone, oral methadone or sublingual buprenorphine were identified via records from a drug and alcohol clinic (Subiaco, WA) for naltrexone and state prescribing records for methadone and buprenorphine. A control cohort of non-opioid-dependent women was obtained from the WA electoral roll. Identifying information and treatment records for these women were linked against the Midwife Notification System records to identify exposed offspring born between 2001 and 2011. Birth characteristics, congenital anomalies and perinatal mortality for all neonates were extracted from state records. The birth characteristics of naltrexone-exposed neonates (n = 68) were superior to methadone-exposed neonates (n = 199) in terms of birth size (birth weight, head circumference and length), hospital length of stay (5.5 vs. 11.3 days), and rates of neonatal abstinence syndrome (NAS) (7.5 vs. 51.5%). Naltrexone-exposed neonates were generally not significantly different to buprenorphine-exposed neonates (n = 124), with the exception of significantly lower rates of NAS (7.5 vs. 41.8%) and shorter hospital length of stay (5.5 vs. 8.0 days) in naltrexone-exposed neonates. Compared with the control group of neonates (n = 569), naltrexone-exposed neonates were not significantly different in terms of overall rates of congenital anomalies, stillbirths and neonatal mortality; however, they were significantly smaller (3137.1 vs. 3378.0 g), spent more time in hospital following birth (5.5 vs. 4.3

  15. COMPARATIVE STUDY BETWEEN INTRATHECAL BUPIVACAINE 0.5% HEAVY + FENTANYL (0.5 MICROGRAMS/KG VERSUS INTRATHECAL BUPIVACAINE 0.5% HEAVY + BUPRENORPHINE (2 MICROGRAMS/KG IN LOWER ABDOMINAL AND LOWER LIMB SURGERIES

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    Naresh Bhukya

    2017-10-01

    Full Text Available BACKGROUND Various adjuvants have been added to bupivacaine to shorten the onset of block and prolong the duration of block. Present study was undertaken to compare the efficacy of intrathecal fentanyl or buprenorphine with bupivacaine for all infraumbilical surgeries. MATERIALS AND METHODS 100 ASA I and II patients of both sexes posted for various infraumbilical surgeries were chosen for the study and the patients were divided into two groups of 50 each. Group F received 3mL of 0.5% bupivacaine heavy with 0.5mcg/kg of fentanyl and groupB received 3mL of 0.5% bupivacaine heavy with 2mcg/kg of buprenorphine. The time of onset of sensory block was tested with pinprick method and motor block was assessed by onset of Bromage scale 3 and it was found that the onset of sensory block with buprenorphine was earlier compared to fentanyl. RESULTS Bradycardia observed in Group B in 7 patients (14%, which was successfully treated with vagolytic agents. In Group B, it was observed that there was hypotension in 14 patients (28%, and in Group F, 7 patients developed hypotension, which was successfully treated with vasopressors. Also, few patients developed pruritus, nausea and vomiting, which were negligible. Intraoperatively, sedation score was assessed using modified Ramsay. Sedation scale and there was higher incidence of sedation with buprenorphine group. Regression of motor block to Bromage0 was observed and the time to regression was significantly prolonged to 205±37.71 in the buprenorphine group, while it was 152.90±8.31 in the fentanyl group. Postoperatively, VAS scores were significantly low for the buprenorphine group when compared with fentanyl. CONCLUSION To summarise, buprenorphine has higher efficacy with intrathecal bupivacaine with prolonged duration of sensory and motor blockade with decreased incidence of side effects, better haemodynamic stability and intraoperative sedation and also analgesic sparing effect in the postoperative period

  16. Memory function in opioid-dependent patients treated with methadone or buprenorphine along with benzodiazepine: longitudinal change in comparison to healthy individuals

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    Rapeli Pekka; Fabritius Carola; Kalska Hely; Alho Hannu

    2009-01-01

    Abstract Background Opioid-substitution treatment (OST) for opioid dependence (OD) has proven effective in retaining patients in treatment and reducing illegal opiate abuse and crime. Consequently, the World Health Organization (WHO) has listed the opioid agonists methadone and buprenorphine as essential drugs for OD that should be available worldwide. In many areas of the world, OD is often associated with concomitant benzodiazepine (BZD) dependence and abuse, which complicates treatment. Ho...

  17. BU08073 a buprenorphine analogue with partial agonist activity at μ-receptors in vitro but long-lasting opioid antagonist activity in vivo in mice.

    Science.gov (United States)

    Khroyan, T V; Wu, J; Polgar, W E; Cami-Kobeci, G; Fotaki, N; Husbands, S M; Toll, L

    2015-01-01

    Buprenorphine is a potent analgesic with high affinity at μ, δ and κ and moderate affinity at nociceptin opioid (NOP) receptors. Nevertheless, NOP receptor activation modulates the in vivo activity of buprenorphine. Structure activity studies were conducted to design buprenorphine analogues with high affinity at each of these receptors and to characterize them in in vitro and in vivo assays. Compounds were tested for binding affinity and functional activity using [(35) S]GTPγS binding at each receptor and a whole-cell fluorescent assay at μ receptors. BU08073 was evaluated for antinociceptive agonist and antagonist activity and for its effects on anxiety in mice. BU08073 bound with high affinity to all opioid receptors. It had virtually no efficacy at δ, κ and NOP receptors, whereas at μ receptors, BU08073 has similar efficacy as buprenorphine in both functional assays. Alone, BU08073 has anxiogenic activity and produces very little antinociception. However, BU08073 blocks morphine and U50,488-mediated antinociception. This blockade was not evident at 1 h post-treatment, but is present at 6 h and remains for up to 3-6 days. These studies provide structural requirements for synthesis of 'universal' opioid ligands. BU08073 had high affinity for all the opioid receptors, with moderate efficacy at μ receptors and reduced efficacy at NOP receptors, a profile suggesting potential analgesic activity. However, in vivo, BU08073 had long-lasting antagonist activity, indicating that its pharmacokinetics determined both the time course of its effects and what receptor-mediated effects were observed. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2014 The British Pharmacological Society.

  18. Pharmacokinetic and pharmacodynamic modelling after subcutaneous, intravenous and buccal administration of a high-concentration formulation of buprenorphine in conscious cats

    Science.gov (United States)

    Doodnaught, Graeme M.; Monteiro, Beatriz P.; Benito, Javier; Edge, Daniel; Beaudry, Francis; Pelligand, Ludovic

    2017-01-01

    Background The aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats. Methods Six healthy cats (4.9 ± 0.7 kg) were included in a prospective, randomized, blinded, crossover study. Simbadol™ (1.8 mg mL-1) was administered by the subcutaneous (SC; 0.24 mg kg-1), intravenous (IV; 0.12 mg kg-1) or buccal (OTM; 0.12 mg kg-1) route of administration and thermal thresholds (TT) were compared with a saline group (SAL). Thermal threshold testing and blood sampling were performed at predetermined time points up to 72 hours including a placebo group. Plasma buprenorphine and norbuprenorphine concentrations were measured using liquid chromatography mass spectrometry. A bespoke bicompartmental pharmacokinetic model simultaneously fitted data from two analytes/three routes of administration. Temporal changes in TT were analyzed using one-way ANOVA followed by Dunnett’s test and treatment comparisons using two-way ANOVA with Bonferroni’s correction (P buprenorphine-treated cats. The absolute buprenorphine clearance was 0.98 L kg-1 hour-1, volume of distribution at steady state was 7.9 L kg-1 and the elimination-half-life was 12.3 hours. Bioavailability for SC and OTM was 94% and 24%, respectively. Subcutaneous absorption was biphasic. An initial peak (0.08 hours) was followed by a slow (half-life 11.2 hours) and progressive (peak acceleration at 2.8 hours) uptake. Conclusion The SC administration of Simbadol™ was characterized by prolonged absorption half-life and sustained plasma concentrations yielding long-lasting antinociception (≥ 24 hours) when compared with the IV and OTM routes. PMID:28445495

  19. Sedative and analgesic effects of buprenorphine, combined with either acepromazine or dexmedetomidine, for premedication prior to elective surgery in cats and dogs.

    Science.gov (United States)

    Hunt, James R; Grint, Nicola J; Taylor, Polly M; Murrell, Joanna C

    2013-05-01

    To evaluate the sedative and analgesic effects of intramuscular buprenorphine with either dexmedetomidine or acepromazine, administered as premedication to cats and dogs undergoing elective surgery. Prospective, randomized, blinded clinical study. Forty dogs and 48 cats. Animals were assigned to one of four groups, according to anaesthetic premedication and induction agent: buprenorphine 20 μg kg(-1) with either dexmedetomidine (dex) 250 μg m(-2) or acepromazine (acp) 0.03 mg kg(-1), followed by alfaxalone (ALF) or propofol (PRO). Meloxicam was administered preoperatively to all animals and anaesthesia was always maintained using isoflurane. Physiological measures and assessments of pain, sedation and mechanical nociceptive threshold (MNT) were made before and after premedication, intraoperatively, and for up to 24 hours after premedication. Data were analyzed with one-way, two-way and mixed between-within subjects anova, Kruskall-Wallis analyses and Chi squared tests. Results were deemed significant if p ≤ 0.05, except where multiple comparisons were performed (p ≤ 0.005). Cats premedicated with dex were more sedated than cats premedicated with acp (p buprenorphine, caused minor, clinically detectable, differences in various characteristics of anaesthesia, but not in the level of analgesia. A combination of buprenorphine with either acp or dex, followed by either PRO or ALF, and then isoflurane, accompanied by an NSAID, was suitable for anaesthesia in dogs and cats undergoing elective surgery. Choice of sedative agent may influence dose of anaesthetic induction agent. © 2012 The Authors. Veterinary Anaesthesia and Analgesia © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  20. Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting.

    Science.gov (United States)

    Hedenqvist, Patricia; Trbakovic, Amela; Thor, Andreas; Ley, Cecilia; Ekman, Stina; Jensen-Waern, Marianne

    2016-08-01

    In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10×10mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n=9) or buprenorphine plus saline (n=9) postoperatively. Buprenorphine was administered subcutaneously every 6h for 3days in a tapered dose (0.05-0.01mg/kg) and carprofen (5mg/kg) or saline administered subcutaneously 1h before, and daily for 4days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 4.3 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5mg/kg carprofen once daily for 5days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti-reward and relapse potential?

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    Blum, Kenneth; Chen, Thomas JH; Bailey, John; Bowirrat, Abdulla; Femino, John; Chen, Amanda LC; Simpatico, Thomas; Morse, Siobhan; Giordano, John; Damle, Uma; Kerner, Mallory; Braverman, Eric R.; Fornari, Frank; Downs, B.William; Rector, Cynthia; Barh, Debmayla; Oscar-Berman, Marlene

    2013-01-01

    Opiate addiction is associated with many adverse health and social harms, fatal overdose, infectious disease transmission, elevated health care costs, public disorder, and crime. Although community-based addiction treatment programs continue to reduce the harms of opiate addiction with narcotic substitution therapy such as methadone maintenance, there remains a need to find a substance that not only blocks opiate-type receptors (mu, delta, etc.) but also provides agonistic activity; hence the impetus arose for the development of a combination of narcotic antagonism and mu receptor agonist therapy. After three decades of extensive research the federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with addiction disorders by providing increased access to options for treatment. DATA allows physicians who complete a brief specialty-training course to become certified to prescribe buprenorphine and buprenorphine/naloxone (Subutex, Suboxone) for treatment of patients with opioid dependence. Clinical studies indicate buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and in reducing illicit opioid use. With that stated, we must consider the long-term benefits or potential toxicity attributed to Subutex or Suboxone. We describe a mechanism whereby chronic blockade of opiate receptors, in spite of only partial opiate agonist action, may ultimately block dopaminergic activity causing anti-reward and relapse potential. While the direct comparison is not as yet available, toxicity to buprenorphine can be found in the scientific literature. In considering our cautionary note in this commentary, we are cognizant that to date this is what we have available, and until such a time when the real magic bullet is discovered, we will have to endure. However, more than anything else this commentary should at least encourage the development of thoughtful new strategies to target the

  2. Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects

    Science.gov (United States)

    Gelston, Eloise A; Coller, Janet K; Lopatko, Olga V; James, Heather M; Schmidt, Helmut; White, Jason M; Somogyi, Andrew A

    2012-01-01

    AIMS To compare the O-demethylation (CYP2D6-mediated), N-demethylation (CYP3A4-mediated) and 6-glucuronidation (UGT2B4/7-mediated) metabolism of codeine between methadone- and buprenorphine-maintained CYP2D6 extensive metabolizer subjects. METHODS Ten methadone- and eight buprenorphine-maintained subjects received a single 60 mg dose of codeine phosphate. Blood was collected at 3 h and urine over 6 h and assayed for codeine, norcodeine, morphine, morphine-3- and -6-glucuronides and codeine-6-glucuronide. RESULTS The urinary metabolic ratio for O-demethylation was significantly higher (P = 0.0044) in the subjects taking methadone (mean ± SD, 2.8 ± 3.1) compared with those taking buprenorphine (0.60 ± 0.43), likewise for 6-glucuronide formation (0.31 ± 0.24 vs. 0.053 ± 0.027; P codeine and norcodeine concentrations (P codeine-6-glucuronide concentrations (P < 0.008). CONCLUSION Methadone is associated with inhibition of CYP2D6 and UGTs 2B4 and 2B7 reactions in vivo, even though it is not a substrate for these enzymes. Plasma morphine was not altered, owing to the opposing effects of inhibition of both formation and elimination; however, morphine-6-glucuronide (analgesically active) concentrations were substantially reduced. Drug interactions with methadone are likely to include drugs metabolized by various UGTs and CYP2D6. PMID:22092298

  3. Postoperative Analgesia Due to Sustained-Release Buprenorphine, Sustained-Release Meloxicam, and Carprofen Gel in a Model of Incisional Pain in Rats (Rattus norvegicus).

    Science.gov (United States)

    Seymour, Travis L; Adams, Sean C; Felt, Stephen A; Jampachaisri, Katechan; Yeomans, David C; Pacharinsak, Cholawat

    2016-01-01

    Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.

  4. Buprenorphine from detox and beyond: preliminary evaluation of a pilot program to increase heroin dependent individuals' engagement in a full continuum of care.

    Science.gov (United States)

    Donovan, Dennis M; Knox, Patricia C; Skytta, Jenny A F; Blayney, Jessica A; DiCenzo, Jessica

    2013-04-01

    Absence of successful transition to post-detoxification treatment leads to high rates of relapse among detoxified heroin users. The present study evaluated a pilot buprenorphine treatment program (BTP). Heroin dependent individuals were inducted onto buprenorphine/naloxone in detox, maintained while transitioning through an intensive inpatient program (IIP), and gradually tapered off medication over 5 months of outpatient (OP) treatment. Compared to programmatic indicators of treatment engagement in the year prior to BTP implementation, referrals from detox to IIP, entry into and completion of IIP and subsequent OP, and days in OP treatment increased substantially. BTP completers, compared to non-completers, viewed abstinence as more difficult and as requiring more assistance to achieve, were less likely to be current cocaine and alcohol users or to have relapsed during the course of treatment. Although preliminary and in need of replication, initial adjunctive use of buprenorphine in an abstinence-based continuum of care may improve post-detoxification treatment entry, engagement, and completion. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Memory function in opioid-dependent patients treated with methadone or buprenorphine along with benzodiazepine: longitudinal change in comparison to healthy individuals.

    Science.gov (United States)

    Rapeli, Pekka; Fabritius, Carola; Kalska, Hely; Alho, Hannu

    2009-04-17

    Opioid-substitution treatment (OST) for opioid dependence (OD) has proven effective in retaining patients in treatment and reducing illegal opiate abuse and crime. Consequently, the World Health Organization (WHO) has listed the opioid agonists methadone and buprenorphine as essential drugs for OD that should be available worldwide. In many areas of the world, OD is often associated with concomitant benzodiazepine (BZD) dependence and abuse, which complicates treatment. However, possible changes in the cognitive functioning of these patients are not well-known. The present study is the first to examine longitudinal stability of memory function in OST patients with BZD use, thus providing a new tool for health policy authorities in evaluating the usefulness of OST. Within the first two months (T1) and between 6-9 months (T2) after OST admission, we followed the working memory, immediate verbal memory, and memory consolidation of 13 methadone- and 15 buprenorphine- or buprenorphine/naloxone-treated patients with BZD dependence or abuse disorder. The results were compared to those of fifteen normal comparison participants. All participants also completed a self-reported memory complaint questionnaire on both occasions. Both patient groups performed statistically significantly worse than normal comparison participants in working memory at time points T1 and T2. In immediate verbal memory, as measured by list learning at T1, patients scored lower than normal comparison participants. Both patient groups reported significantly more subjective memory problems than normal comparison participants. Patients with more memory complaints recalled fewer items at T2 from the verbal list they had learned at T1 than those patients with fewer memory complaints. The significance of the main analyses remained nearly the same when the statistical tests were performed without buprenorphine-only patients leaving 12 patients to buprenorphine/naloxone group. Working memory may be

  6. Memory function in opioid-dependent patients treated with methadone or buprenorphine along with benzodiazepine: longitudinal change in comparison to healthy individuals

    Directory of Open Access Journals (Sweden)

    Rapeli Pekka

    2009-04-01

    Full Text Available Abstract Background Opioid-substitution treatment (OST for opioid dependence (OD has proven effective in retaining patients in treatment and reducing illegal opiate abuse and crime. Consequently, the World Health Organization (WHO has listed the opioid agonists methadone and buprenorphine as essential drugs for OD that should be available worldwide. In many areas of the world, OD is often associated with concomitant benzodiazepine (BZD dependence and abuse, which complicates treatment. However, possible changes in the cognitive functioning of these patients are not well-known. The present study is the first to examine longitudinal stability of memory function in OST patients with BZD use, thus providing a new tool for health policy authorities in evaluating the usefulness of OST. Methods Within the first two months (T1 and between 6–9 months (T2 after OST admission, we followed the working memory, immediate verbal memory, and memory consolidation of 13 methadone- and 15 buprenorphine- or buprenorphine/naloxone-treated patients with BZD dependence or abuse disorder. The results were compared to those of fifteen normal comparison participants. All participants also completed a self-reported memory complaint questionnaire on both occasions. Results Both patient groups performed statistically significantly worse than normal comparison participants in working memory at time points T1 and T2. In immediate verbal memory, as measured by list learning at T1, patients scored lower than normal comparison participants. Both patient groups reported significantly more subjective memory problems than normal comparison participants. Patients with more memory complaints recalled fewer items at T2 from the verbal list they had learned at T1 than those patients with fewer memory complaints. The significance of the main analyses remained nearly the same when the statistical tests were performed without buprenorphine-only patients leaving 12 patients to

  7. Alterações cardiovasculares e intracranianas promovidas pela buprenorfina em cães anestesiados com desflurano Buprenorphine cardiovascular and intracranial alterations in dogs anesthetized with desflurane

    Directory of Open Access Journals (Sweden)

    Almir Pereira de Souza

    2004-06-01

    Full Text Available Objetivou-se com a realização deste experimento, estudar possíveis alterações nas variáveis cardiovasculares e intracranianas promovidas pela buprenorfina, em cães anestesiados com desflurano. Para tanto, foram utilizados oito cães adultos, clinicamente saudáveis. A anestesia foi induzida com propofol (8 mg/kg IV e em seguida os animais foram intubados com sonda orotraqueal de Magill, a qual foi conectada ao aparelho de anestesia volátil para administração de desflurano (1,5 CAM. Os animais foram mantidos sob ventilação controlada durante todo o período experimental. Após 20 minutos do posicionamento do cateter de pressão intracraniana (PIC, administrou-se buprenorfina (0,02 mg/kg IV. Foram avaliados: PIC; pressão de perfusão cerebral (PPC; FC; PAS, PAM e PAD; débito cardíaco (DC; pressão venosa central (PVC; e pressão da artéria pulmonar (PAP. As colheitas foram feitas nos seguintes momentos: M1 - 20 minutos após o posicionamento do cateter de PIC; M2 - 15 minutos após a administração do opióide; M3, M4 e M5 - de 15 em 15 minutos após M2. A avaliação estatística dos dados foi efetuada por meio de ANOVA seguida do Teste de Tukey (pThe aim of this work was to study the possible alterations on cardiovascular and intracranial parameters caused by buprenorphine, in dogs anesthetized with desflurane. Eight adult healthy male and female mongrel dogs were used. The anesthetic induction was made using propofol (IV, and immediately after, the dogs were intubated and the tube was connected to a volatile anesthetic circuit, and desflurane was administrated at 1.5 MAC. The dogs were intrumented and 20 minutes after the introduction of the intracranial catheter, they received buprenorphine (0.02 mg/kg/IV. The animals were on mechanical ventilation during all the experimental period. Intracranial pressure (ICP, cerebral perfusion pressure (CPP, Heart Rate (HR; Systolic, Diastolic and Mean Arterial Blood Pressure (SAP, DAP and

  8. Quality of life of treated opiate addicts in the methadone maintenance program and those treated with buprenorphine

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    Marinković Mirjana

    2017-01-01

    Full Text Available Background/Aim. Although the characteristics of the treatment are the most researched determinants of quality of life of opiate addicts, it is indisputable that there is a certain influence of the characteristics of addicts and addiction, too. The aim of this study was to determine which addicts characteristics, as well as the characteristics of the addiction and treatment have predicative influence on the quality of life of the opiate addicts treated in the methadone maintenance program and those treated with buprenorphine. Methods. The epidemiological cross-sectional study was carried out in 2013 at the Clinical Center Niš, on a total of 64 opiate addicts, both sexes, aged 18 and older (32 addicts in the methadone program, chosen by random selection, and 32 addicts treated with buprenorphine, matched by sex and age. Necessary data were collected in a “face to face” interview with the examinees, based on the autonomous kind of a questionnaire, together with the use of the standardized World Health Organization (WHO instruments: for health status, for the level of severity of addiction and for the quality of life measuring based on which the health index (EQ-5D, Addiction Severity Index (ASI and the quality of life index (WHOQOL-BREF were calculated. The data were described by the methods of descriptive statistics, while the differences between groups were analyzed by applying χ2 and t-test. Multiple regressions were used to determine the predictors. Results. The addicts in the methadone program showed much worse perception of quality of life than those treated in another way, although, according to the values of quality of life, they did not differ significantly. The most numerous predictors of the level of quality of life were health characteristics, characteristics of the socioeconomic position of the examinees, as well as different consequences of addiction. The influence of treatment was less noticeable. Participating in the methadone

  9. [Buprenorphin and benzodiazepines, an association with high risk. Reality of co-prescriptions by the general practitioners].

    Science.gov (United States)

    Di Patrizio, Paolo; Houille, Sophie; Schwan, Raymund; Boivin, Jean-Marc

    2010-12-20

    The buprenorphine (BHD) is an effective maintenance treatment for opioid dependence, used in France until 1996. From 1996 to 2001, it is involved in 137 deaths by respiratory depression including 91 attributable to the benzodiazepines (BDZ) association. The number of deaths caused by the BHD and BDZ, when they are taken jointly, is probably underestimated. The reasons for this association are the misuse, the self-medication and the co-prescription. The objective of this study was to assess the co-prescription of these two drugs by the general practitioners (GPs) of Nancy (France). A survey was conducted during the first semester 2007. Using the datas of the Caisse Primaire d'Assurance Maladie (the French national health service), all the requests for a reimbursement of BHD in Nancy were analysed. 1655 BHD consumers were included in this survey. Thirty-one percent of them asked for the reimbursement of at least one BZD at the same time. The BZD consumers were old, consulted more than one prescriber or chemist and more often consumed high dosages of BHD. The BZD consumption is often associated to BHD intake (31%). GPs need a better training on the subject: "How to take care of patients who depend on opiod". This would reduce the risks. A better information for the BHD users would be necessary as well as a lowest prescription of BZD by the GPs. Before any BHD prescription, the GPs should assess a possible co-dependence to BZD in order to improve the BHD prescription.

  10. Effects of sedation with acepromazine maleate and buprenorphine hydrochloride on femoral artery blood flow in healthy dogs.

    Science.gov (United States)

    Nogueira, R B; Fernández del Palacio, M J; López, J T; Resende, R M

    2012-10-01

    The purpose of this study was to qualify and quantify the femoral artery blood flow by duplex Doppler ultrasonography (DDU) in healthy dogs, before and after the administration of a combination of acepromazine maleate and buprenorphine hydrochloride (ACP-BPN). Seven healthy adult mongrel dogs and three adult beagles were used. Heart rate, arterial blood pressure and measurement of femoral artery blood flow by DDU were also recorded. The DDU measurements were: femoral artery diameter (FAD), peak systolic velocity (PSV), early retrograde (EDV) and end diastolic velocities (EnDV), mean velocity (BMV), pulsatility index (PI), flow velocity integral (FVI) and femoral blood flow (FBF). After 30 min, combination ACP-BPN was administered intramuscularly, and all the measurements were recorded again. The ACP-BPN protocol induced a significant decrease in systolic, mean, and diastolic arterial blood pressure, and heart rate. A significant increase in peak systolic velocity and integral flow velocity integral of the femoral blood were obtained. The Doppler spectra of the blood flow in the femoral artery revealed a spectral dispersion pattern after ACP-BPN administration in all the dogs. These results demonstrate that despite quantitative and qualitative changes, the overall femoral blood flow (FBF) is not significantly modified. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Erectile dysfunction and quality of life in men receiving methadone or buprenorphine maintenance treatment. A cross-sectional multicentre study.

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    Fabio Lugoboni

    Full Text Available Erectile dysfunction (ED is common among men on opioid replacement therapy (ORT, but most previous studies exploring its prevalence and determinants yielded contrasting findings. Moreover, the impact of ED on patients' quality of life (QoL has been seldom explored.To explore the prevalence and determinants of ED in men on ORT, and the impact on QoL.In a multicentre cross-sectional study, we recruited 797 consecutive male patients on methadone and buprenorphine treatment, collected data on demographic, clinical, and psychopathological factors, and explored their role as predictors of ED and QoL through univariate and multivariate analysis. ED severity was assessed with a self-assessment questionnaire.Nearly half of patients in our sample were sexually inactive or reported some degree of ED. Some demographic, clinical and psychopathological variables significantly differed according to the presence or absence of ED. Multivariate regression analysis indicated that age, employment, smoke, psychoactive drugs, opioid maintenance dosage, and severity of psychopathological factors significantly influenced the risk and severity of ED. QoL was worse in patients with ED and significantly correlated with ED severity. Age, education, employment, opioid maintenance dosage, ED score, and severity of psychopathology significantly influenced QoL in the multivariate analysis.ED complaints can be explored in male opioid users on ORT through a simple and quick self-assessment tool. ED may have important effects on emotional and social well-being, and may affect outcome.

  12. A comparative study of extradural anesthesia using 0.75% ropivacaine, 0.75% ropivacaine with fentanyl, and 0.75% ropivacaine with buprenorphine for cesarean section from a rural teaching hospital in India

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    Grace Maria George

    2014-01-01

    Full Text Available Context: The study was to compare the analgesic efficacy of three different epidural solutions - ropivacaine, ropivacaine fentanyl mixture, and ropivacaine buprenorphine mixture - for cesarean section. Materials and Methods: This was a prospective, randomized, controlled, double blind study carried out in primi parturients undergoing elective cesarean section with singleton fetus. A total of 102 parturients in the age group of 20-35 years, American Society of Anesthesiologists (ASA I or II scheduled for elective cesarean under continuous epidural anesthesia were divided into three groups using a computer-generated random number list. The test dose (3 ml 2% lignocaine with 15 μg adrenaline and 0.75% ropivacaine 12 ml were given to all parturients. In addition, normal saline 1 ml, fentanyl 50 μg, and buprenorphine 300 μg were given to Group I, II, and III respectively. Sensory block, motor block, analgesia, maternal effects, fetal outcome, and surgeons′ and parturients′ satisfaction were evaluated. Results: Onset of sensory block was faster in the fentanyl and buprenorphine groups compared to ropivacaine group (9.94 ± 0.48, 10.72 ± 0.26 versus 14.59 ± 0.34. Duration of sensory block was prolonged in buprenorphine group as compared to fentanyl and ropivacaine groups (120.41 ± 4.31 versus (95.68 ± 3.28, 98.28 ± 3.42. Duration of analgesia was prolonged in buprenorphine group compared to fentanyl and ropivacaine groups (516.38 ± 29.14 versus 327.06 ± 12.41, 285.78 ± 10.10. It proved to be safe for mother and fetus. The surgeon and the parturients were satisfied with the mode of anesthesia. Conclusion: Ropivacaine 0.75%, ropivacaine 0.75% with fentanyl 50 mg, or buprenorphine 300 mg provided safe anesthesia when given extradurally for cesarean section. Addition of both fentanyl and buprenorphine to ropivacaine hastened the onset of sensory block, while addition of buprenorphine provided prolonged excellent postoperative analgesia.

  13. Automated radiosyntheses of [6-0-methyl-[sup 11]C]diprenorphine and [6-0-methyl-[sup 11]C]buprenorphine from 3-0-trityl protected precursors

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    Luthra, S.K.; Brady, F.; Turton, D.R.; Brown, D.J.; Dowsett, K.; Waters, S.L.; Jones, A.K.P. (Hammersmith Hospital, London (United Kingdom). M.R.C. Cyclotron Unit); Matthews, R.W.; Crowder, J.C. (North London Univ., London (United Kingdom). School of Applied Chemistry)

    1994-08-01

    The antagonist [6-0-methyl-[sup 11]C]diprenorphine and the mixed agonist/antagonist [6-0-methyl-[sup 11]C]buprenorphine, radioligands for studying the opioid receptor system in vivo with positron emission tomography, were preapred by 0-methylation of (3-0-trityl, 6-desmethyl)diprenorphine and [3-0-trityl,6-desmethyl]buprenorphine, respectively, with [[sup 11]C]iodomethane. The use of the base-stable, acid labile trityl protecting group minimizes the formation of byproducts and allows reproducible radiosyntheses. (author).

  14. Extended release naltrexone injection is performed in the majority of opioid dependent patients receiving outpatient induction: a very low dose naltrexone and buprenorphine open label trial.

    Science.gov (United States)

    Mannelli, Paolo; Wu, Li-Tzy; Peindl, Kathleen S; Swartz, Marvin S; Woody, George E

    2014-05-01

    The approval of extended release injectable naltrexone (XR-NTX; Vivitrol(®)) has introduced a new option for treating opioid addiction, but studies are needed to identify its place within the spectrum of available therapies. The absence of physiological opioid dependence is a necessary and challenging first step for starting XR-NTX. Outpatient detoxification gives poor results and inpatient detoxification is either unavailable or too brief for the physiological effects of opioids to resolve. Here we present findings from an open label study that tested whether the transition from opioid addiction to XR-NTX can be safely and effectively performed in an outpatient setting using very low dose naltrexone and buprenorphine. Twenty treatment seeking opioid addicted individuals were given increasing doses of naltrexone starting at 0.25mg with decreasing doses of buprenorphine starting at 4 mg during a 7-day outpatient XR-NTX induction procedure. Withdrawal discomfort, craving, drug use, and adverse events were assessed daily until the XR-NTX injection, then weekly over the next month. Fourteen of the 20 participants received XR-NTX and 13 completed weekly assessments. Withdrawal, craving, and opioid or other drug use were significantly lower during induction and after XR-NTX administration compared with baseline, and no serious adverse events were recorded. Outpatient transition to XR-NTX combining upward titration of very low dose naltrexone with downward titration of low dose buprenorphine was safe, well tolerated, and completed by most participants. Further studies with larger numbers of subjects are needed to see if this approach is useful for naltrexone induction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Co-relationship between sexual dysfunction and high-risk sexual behavior in patients receiving buprenorphine and naltrexone maintenance therapy for opioid dependence

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    Santosh Ramdurg

    2015-01-01

    Full Text Available Introduction: People suffering from substance dependence suffer from various sexual dysfunctions and are at risk for indulging in various high-risk sexual behaviors and thus are vulnerable to acquire various infections such as HIV/AIDS and other sexually transmitted infections. AIM: The aim of the study was to evaluate the correlation between sexual dysfunction and high-risk sexual behavior in opioid-dependent men receiving buprenorphine and naltrexone maintenance therapy. Materials and Methods: Semi-structured questionnaire, brief male sexual functioning inventory and HIV-risk taking behavior scale was administered to a sample of 60 sexually active men, receiving buprenorphine (n = 30 and naltrexone (n = 30 maintenance therapy for opioid dependence. Results: The main outcomes are correlation between severity of sexual dysfunction and HIV-risk taking behavior. The study results showed 83% of the men on buprenorphine and 90% on naltrexone reported at least one of the sexual dysfunction symptoms. There was a negative correlation between sexual dysfunction and HIV-risk taking behavior that suggest severe the dysfunction, higher the risk taking behavior. Significant correlation was present with overall sexual dysfunction and HIV-risk taking behavior (P = 0.028 and in naltrexone receiving group premature ejaculation versus HIV-risk taking behavior however, (P = 0.022, P < 0.05 there were no significant differences among both the groups except above findings. Conclusion: Conclusion was treatment is associated with sexual dysfunctions and HIV-risk taking behavior, which has clinical implication. Future research should explore this further using biochemical analyses.

  16. Influence of ketamine on the cardiopulmonary effects of intramuscular administration of dexmedetomidine-buprenorphine with subsequent reversal with atipamezole in dogs.

    Science.gov (United States)

    Ko, Jeff C; Barletta, Michele; Sen, Ismail; Weil, Ann B; Krimins, Rebecca A; Payton, Mark E; Constable, Peter

    2013-02-01

    To compare the cardiorespiratory effects of IM administration of dexmedetomidine-buprenorphine (DB) and dexmedetomidine-buprenorphine-ketamine (DBK) in dogs with subsequent reversal with atipamezole. Prospective, randomized crossover study. 5 healthy dogs. Dogs were instrumented for cardiac output (CO) measurement and received DB (15 μg of dexmedetomidine/kg [6.8 μg/lb] and 40 μg of buprenorphine/kg [18.2 μg/lb]) or DBK (DB plus 3 mg of ketamine/kg [1.36 mg/lb]) in randomized order while breathing room air. Atipamezole (150 μg/kg [68.2 μg/lb], IM) was administered 1 hour later. Hemodynamic data were collected in the conscious dogs and then at 5, 10, 15, 20, 30, 45, and 60 minutes after drug administration. Lactate concentration was measured in mixed venous blood samples. Oxygen delivery (Do(2)) and oxygen consumption ([Formula: see text]o(2)) were calculated. Heart rate (HR), CO, and Do(2) decreased after DB and DBK administration. The [Formula: see text]o(2) did not change in the DB group but decreased in the DBK group. The HR was higher in the DBK group than in the DB group throughout the study, but the CO, Do(2), and [Formula: see text]o(2) values were similar for the 2 groups. Blood lactate concentrations remained low (< 1 mmol/L) throughout the study. Arterial hypoxemia and hypercapnea occurred in both groups. Mean arterial blood pressure and pulmonary artery wedge pressure were markedly increased in both groups, but to a greater extent in the DBK group. After atipamezole administration, HR, CO, and Do(2) returned to the baseline values. Adding ketamine to the DB combination allowed dogs to maintain a higher HR and delayed the onset of sinus arrhythmias but failed to provide a significantly higher CO because of a reduction in stroke volume.

  17. The effectiveness of a long-acting transdermal fentanyl solution compared to buprenorphine for the control of postoperative pain in dogs in a randomized, multicentered clinical study.

    Science.gov (United States)

    Linton, D D; Wilson, M G; Newbound, G C; Freise, K J; Clark, T P

    2012-08-01

    A prospective, double-blinded, positive-controlled, multicenter, noninferiority clinical study was conducted to evaluate the safety and effectiveness of a long-acting transdermal fentanyl solution (TFS) for the control of postoperative pain. Four hundred forty-five client-owned dogs of various breeds were randomly assigned to receive a single dose of TFS (2.6 mg/kg [∼50 μL/kg]) (N = 223) applied 2-4 h prior to surgery or buprenorphine (20 μg/kg) (N = 222) administered intramuscularly 2-4 h prior to surgery and every 6 h through 90 h. There were 159 (35.7%) males and 286 (64.3%) females ranging from 0.5 to 16 years of age and 3 to 98.5 kg enrolled. Pain was scored using the modified Glasgow Composite Pain Scale with an a priori dropout criteria of ≥ 8 (20 maximum score). The one-sided upper 95% confidence interval of the mean difference between fentanyl and buprenorphine treatment failures was 5.6%, which was not greater than the a priori selected margin difference of 15%. Adverse events attributed to either treatment were minimal in impact and were approximately equal between groups. Sustained plasma fentanyl concentrations provided by a single pre-emptive dose of TFS are safe and effective and are noninferior to repeated injections of buprenorphine in controlling postoperative pain over 4 days. This long-acting fentanyl formulation provides veterinarians with a novel, registered option for the control of postoperative pain in dogs that improves dosing compliance and potentially mitigates the disadvantages of oral, parenteral, and patch delivered opioids. © 2012 Blackwell Publishing Ltd.

  18. Effect of buprenorphine transdermal patch combined with patientcontrolled intravenous analgesia on the serum pain-related biochemical indexes in elderly patients with intertrochanteric fracture

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    Lei Xu

    2017-09-01

    Full Text Available Objective: To study the effect of buprenorphine transdermal patch combined with patientcontrolled intravenous analgesia on the serum pain-related biochemical indexes in elderly patients with intertrochanteric fracture. Methods: A total of 92 elderly patients with intertrochanteric fracture who received surgical treatment in the hospital between August 2014 and January 2017 were collected and divided into control group (n=46 and observation group (n=46 according to the random number table method. The control group received patient-controlled intravenous analgesia, and the observation group received buprenorphine transdermal patch combined with patient-controlled intravenous analgesia. Differences in serum levels of inflammatory factors, oxidative stress indexes and pain mediators of two groups of patients were measured before and 24h after surgery. Results: Differences in serum levels of inflammatory factors, oxidative stress indexes and pain mediators were not statistically significant between the two groups before surgery; 24 h after surgery, serum IL- 1β, IL-6, IL-8, TNF-α, MDA, SP, PGE2, 5-HT, HA and NPY levels of both groups of patients increased significantly while SOD, TAC and CAT levels decreased significantly, and serum IL-1β, IL-6, IL-8, TNF-α, MDA, SP, PGE2, 5-HT, HA and NPY levels of observation group were lower than those of control group while SOD, TAC and CAT levels were higher than those of control group. Conclusion: Buprenorphine transdermal patch combined with patient-controlled intravenous analgesia can effectively inhibit the expression of pain-related indexes and relieve early postoperative pain intensity in elderly patients with intertrochanteric fracture.

  19. Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child.

    Science.gov (United States)

    Zedler, Barbara K; Mann, Ashley L; Kim, Mimi M; Amick, Halle R; Joyce, Andrew R; Murrelle, E Lenn; Jones, Hendrée E

    2016-12-01

    To assess the safety of buprenorphine compared with methadone to treat pregnant women with opioid use disorder. We searched PubMed, Embase and the Cochrane Library from inception to February 2015 for randomized controlled trials (RCT) and observational cohort studies (OBS) that compared buprenorphine with methadone for treating opioid-dependent pregnant women. Two reviewers assessed independently the titles and abstracts of all search results and full texts of potentially eligible studies reporting original data for maternal/fetal/infant death, preterm birth, fetal growth outcomes, fetal/congenital anomalies, fetal/child neurodevelopment and/or maternal adverse events. We ascertained each study's risk of bias using validated instruments and assessed the strength of evidence for each outcome using established methods. We computed effect sizes using random-effects models for each outcome with two or more studies. Three RCTs (n = 223) and 15 cohort OBSs (n = 1923) met inclusion criteria. In meta-analyses using unadjusted data and methadone as comparator, buprenorphine was associated with lower risk of preterm birth [RCT risk ratio (RR) = 0.40, 95% confidence interval (CI) = 0.18, 0.91; OBS RR = 0.67, 95% CI = 0.50, 0.90], greater birth weight [RCT weighted mean difference (WMD) = 277 g, 95% CI = 104, 450; OBS WMD = 265 g, 95% CI = 196, 335] and larger head circumference [RCT WMD = 0.90 cm, 95% CI = 0.14, 1.66; OBS WMD = 0.68 cm, 95% CI = 0.41, 0.94]. No treatment differences were observed for spontaneous fetal death, fetal/congenital anomalies and other fetal growth measures, although the power to detect such differences may be inadequate due to small sample sizes. Moderately strong evidence indicates lower risk of preterm birth, greater birth weight and larger head circumference with buprenorphine treatment of maternal opioid use disorder during pregnancy compared with methadone treatment, and no greater

  20. Comparing methadone and buprenorphine maintenance with methadone-assisted withdrawal for the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes

    Directory of Open Access Journals (Sweden)

    Lund IO

    2012-02-01

    Full Text Available Ingunn O Lund1, Heather Fitzsimons2, Michelle Tuten2, Margaret S Chisolm2, Kevin E O’Grady3, Hendrée E Jones2,41SERAF-Norwegian Centre for Addiction Research, University of Oslo, Oslo, Norway; 2Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD; 3Department of Psychology, University of Maryland, College Park, MD; 4Substance Abuse Treatment Evaluations and Interventions Research Program, RTI International, Research Triangle Park, NC, USAAbstract: Pregnancy can motivate opioid-dependent women to seek substance abuse treatment. Research has demonstrated that although prenatal exposure to buprenorphine results in less severe neonatal abstinence syndrome (NAS relative to prenatal methadone exposure, the maternal and other neonatal outcomes are similar for the two medications. Maternal and neonatal outcomes for opioid-dependent pregnant women receiving these medications have not been systematically compared with methadone-assisted withdrawal. The present study provides an initial assessment of the relative efficacy of both methadone and buprenorphine maintenance versus methadone-assisted withdrawal in terms of neonatal and maternal delivery outcomes. Data were derived from (1 the MOTHER (Maternal Opioid Treatment: Human Experimental Research study at the Johns Hopkins University Bayview Medical Center (JHBMC, or (2 retrospective records review of women who underwent methadone-assisted withdrawal at the JHBMC during the time period in which participants were enrolled in the MOTHER study. Compared with the methadone maintenance group, the methadone-assisted withdrawal group had a significantly lower mean NAS peak score (Means = 13.7 vs 7.0; P = 0.002, required a significantly lower mean amount of morphine to treat NAS (Means = 82.8 vs 0.2; P < 0.001, had significantly fewer days medicated for NAS (Means = 31.5 vs 3.9; P < 0.001, and remained in the hospital for a significantly fewer number of

  1. Effect of buprenorphine on pancreatic enzyme synthesis and secretion in normal rats and rats with acute edematous pancreatitis.

    Science.gov (United States)

    Ogden, J M; Modlin, I M; Gorelick, F S; Marks, I N

    1994-11-01

    Pancreatic enzyme secretion is inhibited during acute pancreatitis, resulting in an increase in acinar zymogen content. Since the premature activation of zymogens has been assigned a central role in the pathogenesis of acute pancreatitis, minimizing the amount of stored zymogens might lead to less severe acute pancreatitis. Inhibition of enzyme synthesis or stimulation of enzyme secretion would result in reduction of zymogen stores. Opiates have a varying effect on pancreatic secretion, depending on the dosage, site of administration, and presence of pancreatic stimulants. The effect of opiates and acute pancreatitis on individual pancreatic enzyme synthesis is unknown. The following study was undertaken in order to examine the effects of an opiate on pancreatic enzyme secretion and synthesis during experimental acute pancreatitis. Four groups of rats were studied. Group I received cerulein (25 micrograms/kg); group II received an opiate, buprenorphine (BPN, 0.5 mg/kg); and group III received cerulein and BPN. Drugs were dissolved in gelatin/saline and injected subcutaneously. A control group (group IV) received only gelatin/saline. Rats were sacrificed 4 hr after injection, and pancreatic mass was measured. Pancreatic acini were prepared and assayed for amylase and DNA content. Amylase, trypsinogen, chymotrypsinogen and lipase synthesis, and amylase secretion were measured for 2 hr. Results showed that, compared to controls, acini of rats with AP had increased amylase content, a finding consistent with decreased in vivo amylase secretion. Total protein and individual enzyme synthesis rates were significantly lower in the acini of the rats with AP than in those of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Retention on buprenorphine is associated with high levels of maximal viral suppression among HIV-infected opioid dependent released prisoners.

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    Sandra A Springer

    Full Text Available HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD.From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART for released HIV-infected prisoners; 50 (53% selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47% selected no BPN/NLX therapy. Maximum viral suppression (MVS, defined as HIV-1 RNA<50 copies/mL, was compared for the BPN/NLX and non-BPN/NLX (N = 44 groups.The two groups were similar, except the BPN/NLX group was significantly more likely to be Hispanic (56.0% v 20.4%, from Hartford (74.4% v 47.7% and have higher mean global health quality of life indicator scores (54.18 v 51.40. MVS after 24 weeks of being released was statistically correlated with 24-week retention on BPN/NLX [AOR = 5.37 (1.15, 25.1], having MVS at the time of prison-release [AOR = 10.5 (3.21, 34.1] and negatively with being Black [AOR = 0.13 (0.03, 0.68]. Receiving DAART or methadone did not correlate with MVS.In recognition that OD is a chronic relapsing disease, strategies that initiate and retain HIV-infected prisoners with OD on BPN/NLX is an important strategy for improving HIV treatment outcomes as a community transition strategy.

  3. Efficacy and Safety of Transdermal Buprenorphine versus Oral Tramadol/Acetaminophen in Patients with Persistent Postoperative Pain after Spinal Surgery

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    Jae Hyup Lee

    2017-01-01

    Full Text Available Purpose. Control of persistent pain following spinal surgery is an unmet clinical need. This study compared the efficacy and safety of buprenorphine transdermal system (BTDS to oral tramadol/acetaminophen (TA in Korean patients with persistent, moderate pain following spinal surgery. Methods. Open-label, interventional, randomized multicenter study. Adults with persistent postoperative pain (Numeric Rating Scale [NRS] ≥ 4 at 14–90 days postsurgery were enrolled. Patients received once-weekly BTDS (n=47; 5 μg/h titrated to 20 μg/h or twice-daily TA (n=40; tramadol 37.5 mg/acetaminophen 325 mg, one tablet titrated to 4 tablets for 6 weeks. The study compared pain reduction with BTDS versus TA at week 6. Quality of life (QoL, treatment satisfaction, medication compliance, and adverse events (AEs were assessed. Findings. At week 6, both groups reported significant pain reduction (mean NRS change: BTDS −2.02; TA −2.76, both P<0.0001 and improved QoL (mean EQ-5D index change: BTDS 0.10; TA 0.19, both P<0.05. The BTDS group achieved better medication compliance (97.8% versus 91.0%. Incidence of AEs (26.1% versus 20.0% and adverse drug reactions (20.3% versus 16.9% were comparable between groups. Implications. For patients with persistent pain following spinal surgery, BTDS is an alternative to TA for reducing pain and supports medication compliance. This trial is registered with Clinicaltrials.gov: NCT01983111.

  4. Use of conventional, complementary, and alternative treatments for pain among individuals seeking primary care treatment with buprenorphine-naloxone

    Science.gov (United States)

    Barry, Declan T.; Savant, Jonathan D.; Beitel, Mark; Cutter, Christopher J.; Moore, Brent A.; Schottenfeld, Richard S.; Fiellin, David A.

    2012-01-01

    Previous studies have not examined patterns of pain treatment use among patients seeking office-based buprenorphine-naloxone treatment (BNT) for opioid dependence. Objectives To examine, among individuals with pain seeking BNT for opioid dependence, the use of pain treatment modalities, perceived efficacy of prior pain treatment, and interest in pursuing pain treatment while in BNT. Methods 244 patients seeking office-based BNT for opioid dependence completed measures of demographics, pain status (i.e. “chronic pain (CP)” [pain lasting at least 3 months] vs. “some pain (SP)” [pain in the past week not meeting the duration criteria for chronic pain]), pain treatment use, perceived efficacy of prior pain treatment, and interest in receiving pain treatment while in BNT. Results In comparison to the SP group (N = 87), the CP group (N = 88) was more likely to report past-week medical use of opioid medication (AOR 3.2, 95% CI 1.2–8.4), lifetime medical use of non-opioid prescribed medication (AOR 2.2, 95% CI 1.1–4.7), and lifetime use of prayer (AOR 2.8, 95% CI 1.2–6.5), and was less likely to report lifetime use of yoga (AOR 0.2, 95% CI 0.1–0.7) to treat pain. While the two pain groups did not differ on levels of perceived efficacy of prior lifetime pain treatments, in comparison to the SP group, the CP group was more likely to report interest in receiving pain treatment while in BNT (P < 0.001). Conclusions Individuals with pain seeking BNT for opioid dependence report a wide range of conventional, complementary, and alternative pain-related treatments and are interested (especially those with CP) in receiving pain management services along with BNT. PMID:23041680

  5. Meloxicam and Buprenorphine Treatment after Ovarian Transplantation Does Not Affect Estrous Cyclicity and Follicular Integrity in Aged CBA/J Mice

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    Le, Anna H.; Bonachea, Luis A.; Cargill, Shelley L.

    2014-01-01

    Angiogenesis, the formation of new blood vessels, is important for the survival of ovarian transplants and the restoration of ovarian functions. Without angiogenesis, transplanted ovarian tissue becomes more susceptible to tissue damage and necrosis. Administration of analgesics for pain management has been shown to decrease angiogenesis, which can influence transplant success especially in aged animals. Aging and the effects of hypoxia after transplantation decrease reproductive viability of the ovarian transplant; therefore, it is important to understand the additional effects of analgesics on aged animal models. The present study investigated the effects of two analgesics, buprenorphine, an opiate, and meloxicam, a non-steroidal anti-inflammatory drug (NSAID), on the reproductive indicators related to estrous cyclicity and follicular integrity after ovarian transplantation of young ovaries into aged CBA/J mice. These aged females did not show any different reproductive responses when treated with either buprenorphine or meloxicam. No significant differences were observed in estrous cycle length, the onset of estrous cycling, the regularity of estrous cycles, and the proportion of viable follicles and total number of follicles per ovarian sample across treatment groups. PMID:25153315

  6. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS prisons project pilot study: protocol for a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification

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    Dalton Richard

    2007-01-01

    Full Text Available Abstract Background In the United Kingdom (UK, there is an extensive market for the class 'A' drug heroin. Many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are buprenorphine, dihydrocodeine and methadone. However, national guidelines do not state a detoxification drug of choice. Indeed, there is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address the paucity by evaluating routinely used interventions amongst drug using prisoners within UK prisons. Methods/Design The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS Prisons Pilot Study will use randomised controlled trial methodology to compare the open use of buprenorphine and dihydrocodeine for opiate detoxification, given in the context of routine care, within HMP Leeds. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome measure will be abstinence status at five days post detoxification, as determined by a urine test. Secondary outcomes during the detoxification and then at one, three and six months post detoxification will be recorded.

  7. Opioid substitution treatment with sublingual buprenorphine in Manipur and Nagaland in Northeast India: what has been established needs to be continued and expanded

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    Sharma Charan

    2009-02-01

    Full Text Available Abstract Manipur and Nagaland in northeast India report an antenatal HIV prevalence of > 1% and the current HIV prevalence among injecting drug users is 24% and 4.5% respectively. Through support from DFID's Challenge Fund, Emmanuel Hospital Association (EHA established thirteen drop-in-centres across the two states to deliver opioid substitution treatment with sublingual buprenorphine for 1200 injecting drug users. Within a short span of time the treatment has been found to be attractive to the clients and currently 1248 injecting opioid users are receiving opioid substitution treatment. The project is acceptable to the drug users, the families, the communities, religious as well as the militant groups. The treatment centres operate all days of the week, have trained staff members, utilize standardized protocols and ensure a strict supervised delivery system to prevent illicit diversion of buprenorphine. The drug users receiving the substitution treatment are referred to HIV voluntary counselling and testing. As this treatment has the potential to change HIV related risk behaviours, what has been established in the two states needs to be continued and expanded with the support from the Government of India.

  8. Pain and Associated Substance Use among Opioid Dependent Individuals Seeking Office-Based Treatment with Buprenorphine-Naloxone: A Needs Assessment Study

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    Barry, Declan T.; Savant, Jonathan D.; Beitel, Mark; Cutter, Christopher J.; Moore, Brent A.; Schottenfeld, Richard S.; Fiellin, David A.

    2012-01-01

    Background and Objectives A paucity of studies has examined the pain experiences of opioid dependent individuals seeking office-based buprenorphine-naloxone treatment (BNT). We set out to examine, among those seeking BNT: (a) the prevalence of pain types (i.e., recent pain, chronic pain), (b) the characteristics of pain (intensity, frequency, duration, interference, location, and genesis), and (c) substance use to alleviate pain. Methods We surveyed 244 consecutive individuals seeking office-based buprenorphine-naloxone treatment (BNT) for opioid dependence about physical pain and associated substance use. Results Thirty-six percent of respondents reported chronic pain (CP) (i.e., pain lasting at least 3 months) and 36% reported “some pain” (SP) (i.e., past week pain not meeting the threshold for CP). In comparison to SP respondents, those with CP were, on average, older; reported greater current pain intensity, pain frequency, typical pain duration, typical pain intensity, and typical pain interference; were more likely to report shoulder or pelvis and less likely to report stomach or arms as their most bothersome pain location; and were more likely to report accident or nerve damage and less likely to report opioid withdrawal as the genesis of their pain. Both pain subgroups reported similarly high rates of past-week substance use to alleviate pain. Conclusions and Scientific Significance The high rates of pain and self-reported substance use to manage pain suggest the importance of assessing and addressing pain in BNT patients. PMID:23617861

  9. The effect of an electronic medicine dispenser on diversion of buprenorphine-naloxone-experience from a medium-sized Finnish city.

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    Uosukainen, Hanna; Pentikäinen, Hannu; Tacke, Ulrich

    2013-07-01

    Providing unobserved opioid substitution treatment (OST) safely is a major challenge. This study examined whether electronic medicine dispensers (EMDs) can reduce diversion of take-home buprenorphine-naloxone (BNX) in a medium-sized Finnish city. All BNX treated OST patients in Kuopio received their take-home BNX in EMDs for 4months. EMDs' effect on diversion was investigated using questionnaires completed by patients (n=37) and treatment staff (n=19), by survey at the local needle exchange service and by systematic review of drug screen data from the Kuopio University Hospital. The majority of patients (n=21, 68%) and treatment staff (n=11, 58%) preferred to use EMDs for the safe storage of tablets. Five patients (16%) declared that EMDs had prevented them from diverting BNX. However, EMDs had no detectable effect on the availability or origin of illegal BNX or on the hospital-treated buprenorphine-related health problems. EMDs may improve the safety of storage of take-home BNX, but their ability to prevent diversion needs further research. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. A comparison of buprenorphine induction strategies: patient-centered home-based inductions versus standard-of-care office-based inductions.

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    Cunningham, Chinazo O; Giovanniello, Angela; Li, Xuan; Kunins, Hillary V; Roose, Robert J; Sohler, Nancy L

    2011-06-01

    Although novel buprenorphine induction strategies are emerging, they have been inadequately studied. To examine our newly developed patient-centered home-based inductions, we conducted a subgroup analysis of 79 opioid-dependent individuals who had buprenorphine inductions at an urban community health center. Participants chose their induction strategy. Standard-of-care office-based inductions were physician driven, with multiple assessments, and observed, and the patient-centered home-based inductions emphasized patient self-management and included a "kit" for induction at home. We conducted interviews and extracted medical records. Using mixed nonlinear models, we examined associations between induction strategy and opioid use and any drug use. Compared with those with standard-of-care office-based inductions, participants with patient-centered home-based inductions had no significant differences in opioid use (adjusted odds ratio [AOR] = 0.63, 95% confidence interval [CI] = 0.13-2.97) but greater reductions in any drug use (AOR = 0.05, 95% CI = 0.01-0.37). Taking into account the limitations of our observational cohort study design, we conclude that participants with patient-centered home-based inductions had similar reductions in opioid use and greater reductions in any drug use than those with standard-of-care office-based inductions. It is essential that new induction strategies be based on existing models or theories and be well studied. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. A study to evaluate buprenorphine at 40 μg kg(-1) compared to 20 μg kg(-1) as a post-operative analgesic in the dog.

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    Slingsby, Louisa S; Taylor, Polly M; Murrell, Joanna C

    2011-11-01

    Comparison of the analgesic effect of buprenorphine at 20 or 40 μg kg(-1) . An investigator 'blinded', randomised study. Twenty six dogs presented for ovariohysterectomy. Dogs were premedicated intramuscularly with acepromazine 0.03 mg kg(-1) and buprenorphine at either 20 (B20, n = 12) or 40 μg kg(-1) (B40, n = 14) followed by anaesthetic induction with propofol and maintenance with isoflurane. During anaesthesia non invasive blood pressure, heart rate, respiratory rate, blood oxygen saturation, inspired and expired volatile agent, end-tidal carbon dioxide and ECG were recorded. Pain and sedation were assessed using interactive VAS scores; mechanical nociceptive thresholds were measured at the wound and hindlimb--all were assessed before and up to 22 hours after administration. Carprofen was used for rescue analgesia. There were no significant differences between the two groups for any of the parameters examined. Rescue analgesia was required around 5 hours after administration of buprenorphine in a significant number of animals. Sedation was good preoperatively and scores decreased over time postoperatively. Hock thresholds did not change over time; wound thresholds decreased significantly compared to the baseline value from 3 hours onwards. Administration of buprenorphine at either 20 or 40 μg kg(-1) IM with acepromazine provided good pre-operative sedation. Cardiovascular and respiratory values remained within clinically acceptable limits during anaesthesia. There was no evidence that increasing dose increased adverse events that may be associated with opioid administration (e.g. bradycardia and respiratory depression). Increasing the dose of buprenorphine from 20 to 40 μg kg(-1) did not provide any benefits with respect to analgesia after ovariohysterectomy as assessed using the VAS scoring system. © 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College

  12. Expanding substance use treatment options for HIV prevention with Buprenorphine-Naloxone: HIV Prevention Trials Network 058 (HPTN 058)

    Science.gov (United States)

    Metzger, David S.; Donnell, Deborah; Celentano, David D.; Jackson, J. Brooks; Shao, Yiming; Aramrattana, Apinun; Wei, Liu; Fu, Liping; Ma, Jun; Lucas, Gregory M.; Chawarski, Marek; Ruan, Yuhua; Richardson, Paul; Shin, Katherine; Chen, Ray Y.; Sugarman, Jeremy; Dye, Bonnie J.; Rose, Scott M.; Beauchamp, Geetha; Burns, David N.

    2015-01-01

    Background Injection opioid use plays a significant role in the transmission of HIV infection in many communities and several regions of the world. Access to evidence-based treatments for opioid use disorders is extremely limited. Methods HPTN 058 was a randomized controlled trial designed to compare the impact of two medication assisted treatment (MAT) strategies on HIV incidence or death among opioid dependent people who inject drugs (PWID). HIV-negative opiate dependent PWID were recruited from four communities in Thailand and China with historically high prevalence of HIV among PWID. 1251 participants were randomly assigned to either; 1) a one year intervention consisting of two opportunities for a 15 day detoxification with buprenorphine/naloxone (BUP/NX) combined with up to 21 sessions of behavioral drug and risk counseling (Short Term Medication Assisted Treatment: ST-MAT) or, 2) thrice weekly dosing for 48 weeks with BUP/NX and up to 21 counseling sessions (Long Term Medication Assisted Treatment: LT-MAT) followed by dose tapering. All participants were followed for 52 weeks after treatment completion to assess durability of impact. Results While the study was stopped early due to lower than expected occurrence of the primary endpoints, sufficient data were available to assess the impact of the interventions on drug use and injection related risk behavior. At weeks 26, 22% of ST-MAT participants had negative urinalyses for opioids compared to 57% in the LT-MAT (p<0.001). Differences disappeared in the year following treatment: at week 78, 35% in ST-MAT and 32% in the LT-MAT had negative urinalyses. Injection related risk behaviors were significantly reduced in both groups following randomization. Conclusions Participants receiving BUP/NX three times weekly were more likely to reduce opioid injection while on active treatment. Both treatment strategies were considered safe and associated with reductions in injection related risk behavior. These data support

  13. Use of immediate-release opioids as supplemental analgesia during management of moderate-to-severe chronic pain with buprenorphine transdermal system

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    Silverman S

    2017-05-01

    Full Text Available Sanford Silverman,1,2 Robert B Raffa,3,4 Marc J Cataldo,5 Monica Kwarcinski,5 Steven R Ripa5 1Comprehensive Pain Medicine, Pompano Beach, 2Department of Integrated Medical Sciences, Charles E Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, 3Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA, 4Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, 5Purdue Pharma LP, Stamford, CT, US Background: The buprenorphine transdermal system (BTDS is approved in the US for the management of chronic pain. Due to its high affinity for μ-opioid receptors with a slow dissociation profile, buprenorphine may potentially displace or prevent the binding of competing μ-opioid-receptor agonists, including immediate-release (IR opioids, in a dose-dependent manner. Health care professionals may assume that the use of IR opioids for supplemental analgesia during BTDS therapy is not acceptable.Materials and methods: This post hoc analysis evaluated the use of IR opioids as supplemental analgesia during the management of moderate–severe chronic pain with BTDS at 52 US sites (BUP3015S, NCT01125917. Patients were categorized into IR-opioid and no-IR-opioid groups. At each visit of the extension phase, adverse events, concomitant medications, and information from the Brief Pain Inventory (BPI were recorded.Results: The most common supplemental IR opioids prescribed during BTDS treatment (n=354 were hydrocodone–acetaminophen and oxycodone–acetaminophen. The mean daily dose of IR opioids (morphine equivalents for supplemental analgesia was 22 mg. At baseline, BPI – pain intensity and BPI – interference scores were higher for patients in the IR-opioid group. In both treatment groups, scores improved by week 4, and then were maintained throughout 6 months of the open-label extension trial. The incidence of treatment-emergent adverse events was similar in

  14. Buprenorphine Transdermal System Improves Sleep Quality and Reduces Sleep Disturbance in Patients with Moderate-to-Severe Chronic Low Back Pain: Results from Two Randomized Controlled Trials.

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    Yarlas, Aaron; Miller, Kate; Wen, Warren; Lynch, Shau Yu; Ripa, Steven R; Pergolizzi, Joseph V; Raffa, Robert B

    2016-03-01

    To evaluate the impact of buprenorphine (Butrans®) transdermal System (BTDS) treatment on sleep outcomes for patients with moderate-to-severe chronic low back pain (CLBP). Two enriched-enrollment, randomized-withdrawal, double-blind, controlled trials examined BTDS treatment for patients with moderate-to-severe CLBP. Trial I evaluated BTDS 10 and 20 mcg/hour against a placebo control among opioid-naïve patients. Trial II compared BTDS 20 mcg/hour against a lower-dose control (BTDS 5 mcg/hour) among opioid-experienced patients. The patient-reported Medical Outcomes Study Sleep Scale (MOS-SS) assessed overall sleep quality (Sleep Problems Index [SPI]), Disturbance, and other sleep outcomes. In each trial, MOS-SS scores were compared between target treatment and control arms during the 12-week double-blind phase. Correspondence of changes in sleep outcomes and pain severity and the degree to which pain reduction mediates treatment impact on sleep outcomes were examined. Medical Outcomes Study Sleep Scale scores were collected from 541 (Trial I) and 441 (Trial II) patients prior to randomization and from 369 (Trial I) and 274 (Trial II) patients at week 12. Patients receiving target treatment showed statistically significantly more improvement in SPI and Disturbance scores at 12 weeks than their respective controls (Ps sleep outcomes. Buprenorphine Transdermal System improved sleep quality and disturbance for opioid-naïve and opioid-experienced patients with moderate-to-severe CLBP. Benefits of BTDS for these sleep outcomes emerged within 4 weeks and were maintained over the entire 12-week treatment period. © 2015 Optum. Pain Practice published by Wiley Periodicals, Inc. on behalf of World Institute of Pain.

  15. Antinociceptive effects of intravenous administration of hydromorphone hydrochloride alone or followed by buprenorphine hydrochloride or butorphanol tartrate to healthy conscious cats.

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    Simon, Bradley T; Steagall, Paulo V; Monteiro, Beatriz P; Troncy, Eric; Lizarraga, Ignacio

    2016-03-01

    To evaluate antinociceptive effects of IV administration of hydromorphone alone or followed by buprenorphine or butorphanol to cats. 6 healthy adult cats. In a randomized, blinded crossover design, cats received each of 4 treatments in which 2 IV injections were given 30 minutes apart: 2 of saline (0.9% NaCl) solution (Sal-Sal) or 1 each of hydromorphone HCl and saline solution (H-Sal), hydromorphone and buprenorphine HCl (H-Bupre), or hydromorphone and butorphanol tartrate (H-Butor). Skin temperature and thermal threshold were recorded before (baseline) and for 12 hours after the first injection. Percentage of maximum possible effect (%MPE) and thermal excursion (TE) were compared among treatments and measurement points. Compared with baseline values, skin temperature was higher from 0.75 to 2 hours after the first injection for H-Sal; at 0.5, 1, 3, and 4 hours for H-Bupre; from 0.5 to 3 hours for H-Butor; and from 0.5 to 1 hours for Sal-Sal. Thermal excursion was higher than at baseline from 0.25 to 2 hours for H-Sal and H-Bupre and 0.25 to 0.75 hours for H-Butor; %MPE increased from 0.25 to 2 hours for H-Sal, 0.25 to 3 hours for H-Bupre, and 0.25 to 0.75 hours for H-Butor. Results were similar for comparisons with Sal-Sal, except TE was greater for H-Sal versus Sal-Sal and TE and %MPE were greater for H-Bupre versus Sal-Sal from 0.25 to 1 hours after the first injection. Butorphanol administration decreased the duration of antinociception achieved with hydromorphone administration in cats. This opioid interaction and its impact on pain management require additional investigation.

  16. Development and application of carbon nanotubes assisted electromembrane extraction (CNTs/EME) for the determination of buprenorphine as a model of basic drugs from urine samples.

    Science.gov (United States)

    Hasheminasab, Kobra Sadat; Fakhari, Ali Reza

    2013-03-12

    In this work carbon nanotubes assisted electromembrane extraction (CNTs/EME) coupled with capillary electrophoresis (CE) and ultraviolet (UV) detection was developed for the determination of buprenorphine as a model of basic drugs from urine samples. Carbon nanotubes reinforced hollow fiber was used in this research. Here the CNTs serve as a sorbent and provide an additional pathway for solute transport. The presence of CNTs in the hollow fiber wall increased the effective surface area and the overall partition coefficient on the membrane; and lead to an enhancement in the analyte transport. For investigating the influence of the presence of CNTs in the SLM on the extraction efficiency, a comparative study was carried out between EME and CNTs/EME methods. Optimization of the variables affecting these methods was carried out in order to achieve the best extraction efficiency. Optimal extractions were accomplished with NPOE as the SLM, with 200V as the driving force, and with pH 2.0 in the donor and pH 1.0 in the acceptor solutions with the whole assembly agitated at 750rpm after 25min and 15min for EME and CNTs/EME, respectively. Under the optimized conditions, in comparison with the conventional EME method, CNTs/EME provided higher extraction efficiencies in shorter time. This method provided lower limit of detection (1ngmL(-1)), higher preconcentration factor (185) and higher recovery (92). Finally, the applicability of this method was evaluated by the extraction and determination of buprenorphine in patients' urine samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Safety and efficacy of transdermal buprenorphine versus oral tramadol for the treatment of post-operative pain following surgery for fracture neck of femur: A prospective, randomised clinical study

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    Sameer N Desai

    2017-01-01

    Full Text Available Background: Transdermal buprenorphine, which is used in chronic pain management, has rarely been studied for use in acute pain management. The aim of this study was to compare the safety and efficacy of transdermal buprenorphine patch to oral tramadol for post-operative analgesia, following proximal femur surgeries. Methodology: Fifty adult patients undergoing surgery for hip fracture under spinal anaesthesia were included in this study. One group (Group TDB received transdermal buprenorphine 10 mcg/h patch applied a day before the surgery and other group received oral tramadol 50 mg three times a day for analgesia (Group OT. They were allowed to take diclofenac and paracetamol tablets for rescue analgesia. Pain scores at rest, on movement, rescue analgesic requirement and side effects were compared between the groups over 7 days. Chi-square and independent sample t-test were used for categorical and continuous variables, respectively. Results: Resting pain scores and pain on movement were significantly lower in TDB Group on all 7 days starting from 24 h post-operatively. Rescue analgesic requirement was significantly lower in TDB Group compared to OT Group. All the patients needed rescue analgesic in OT Group whereas 68% of the patients needed the same in TDB Group. Incidence of vomiting was less and satisfaction scores were much higher in TDB Group as compared to OT Group (79% vs. 66%, P < 0.001. Conclusion: Transdermal buprenorphine can be safely used for post-operative analgesia and is more efficacious in reducing post-operative pain after 24 hours, with fewer side effects when compared to oral tramadol.

  18. Efeitos cardiorrespiratórios da buprenorfina em cães anestesiados pelo desfluorano Cardiorespiratory effects of buprenorphine in dogs anesthetized with desflurane

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    Almir Pereira de Souza

    2005-12-01

    Full Text Available Objetivou-se, com este estudo, avaliar os efeitos da buprenorfina sobre variáveis cardiovasculares e respiratórias em cães durante anestesia com desfluorano. Para tanto, foram utilizados 20 cães adultos, distribuídos em dois grupos (GB e GC. A anestesia foi induzida com propofol (8mg kg-1 IV e em seguida os animais foram intubados com sonda de Magill, a qual foi conectada ao aparelho de anestesia para administração de desfluorano (1,5 CAM. Após 30 minutos, foi aplicado no GB buprenorfina (0,02mg kg-1 e no GC solução de NaCl à 0,9% (0,05ml kg-1. Avaliaram-se: freqüências cardíaca e respiratória (FC e ¦; pressões arteriais sistólica, diastólica e média (PAS, PAD e PAM; débito cardíaco (DC; pressão venosa central (PVC; e as variáveis hemogasométricas pH, PaCO2, PaO2, HCO3, SatO2 e DB. As colheitas dos dados foram feitas aos 30 minutos após o início da administração do desfluorano (MO, 15 minutos após a administração do opióide ou placebo (M15, e a cada 15 minutos após Ml5 (M30, M45, M60 e M75. A avaliação estatística dos dados foi efetuada por meio de Análise de Perfil (P¦ e o pH tiveram reduções no GB, enquanto a PaCO2 esteve aumentada. Concluiu-se que a inclusão da buprenorfina durante anestesia inalatória pelo desfluorano determina discretas alterações cardiovasculares, bem-como potencializa a hipoventilação promovida pelo desfluorano, com a manifestação de hipercapnia, o que não contra-indica o seu uso em pacientes estáveis.The aim of this study was to evaluate the effects of buprenorphine on cardiovascular and respiratory variables in dogs anesthetized with desflurane. Twenty adult healthy male and female mongrel dogs were randomly distributed in two groups of ten animals each (GB and GC. The anesthetic induction was done using propofol (8mg kg-1, IV, and immediately, the dogs were intubated and submited to desflurane anesthesia administrated at 1.5 MAC. After 30 minutes of induction, animals

  19. A comparison of oral controlled-release morphine and oxycodone with transdermal formulations of buprenorphine and fentanyl in the treatment of severe pain in cancer patients

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    Nosek K

    2017-08-01

    Full Text Available Krzysztof Nosek,1 Wojciech Leppert,2,3 Hanna Nosek,4 Jerzy Wordliczek,5 Dariusz Onichimowski6 1Non–public Saint Lazarius Health Care Unit, Biskupiec, 2Chair and Department of Palliative Medicine, Poznan University of Medical Sciences, Poznań, 3Department of Quality of life Research, Gdańsk Medical University, Gdańsk, 4Department of Paediatrics, Regional Children Specialized Hospital, Olsztyn, 5Department of Interdisciplinary Intensive Care, Jagiellonian University College of Medicine, Kraków, 6Department of Intensive Care, Regional Hospital, Olsztyn, Poland Aim of the study: To compare analgesia and adverse effects during oral morphine and oxycodone and transdermal fentanyl and buprenorphine administration in cancer patients with pain. Patients and methods: Cancer patients treated at home and in outpatient clinics with severe pain (numerical rating scale score 6–10 fail to respond to non-opioids and/or weak opioids. All patients were randomized to either morphine, oxycodone, fentanyl or buprenorphine and divided into subgroups with predominant neuropathic and nociceptive pain component. Doses of opioids were titrated to satisfactory analgesia and acceptable adverse effects intensity. Patients were assessed at baseline and followed for 28 days. In all patient groups, immediate-release oral morphine was the rescue analgesic and lactulose 10 mL twice daily was the prophylaxis of constipation; no antiemetics were used as prophylaxis. Results: A total of 62 patients participated and 53 patients completed the study. Good analgesia was obtained for all 4 opioids, for both nociceptive and neuropathic pain. The use of co-analgesics was greater in patients with neuropathic pain. Morphine treatment was associated with less negative impact of pain on ability to walk, work and activity (trend according to Brief Pain Inventory-Short Form scores and less consumption of rescue morphine. The most common adverse effects included nausea and drowsiness

  20. Design of a randomized controlled trial of extended-release naltrexone versus daily buprenorphine-naloxone for opioid dependence in Norway (NTX-SBX).

    Science.gov (United States)

    Kunøe, Nikolaj; Opheim, Arild; Solli, Kristin Klemmetsby; Gaulen, Zhanna; Sharma-Haase, Kamni; Latif, Zill-E-Huma; Tanum, Lars

    2016-04-28

    Current guidelines for opioid dependence recommend daily maintenance of physical dependence with methadone or buprenorphine, and discourage abstinence due to the high risk of relapse and overdose. Extended-release formulations of the opioid antagonist naltrexone (XR-NTX) block heroin and other opioid agonists competitively for around 4 weeks per administration. XR-NTX thus enables opioid users to experience abstinence from opioid agonists with greatly reduced risk of overdose compared to medication-free abstinence. While XR-NTX has shown promise compared to placebo and daily naltrexone tablets, there is limited information on long-term safety and its performance compared to daily maintenance treatment. In this five-hospital RCT with long-term follow-up, we aim to recruit n = 180 patients in treatment for opioid dependence and allocate them in an open, randomized manner (1:1) to receive either 4-week XR-NTX or daily buprenorphine-naloxone (BP-NLX) for the duration of 12 weeks. Allocation is open-label due to the risk of overdose during attempts to self-unmask allocation using heroin. Urine drug tests are scheduled every week with follow-up visits & assessment every 4 weeks. Primary outcomes are abstinence from illicit opioids in urine drug tests and self-report, as well as retention in treatment. Secondary outcomes include other substance use, injecting behavior, drug craving, mental health, quality of life, treatment satisfaction, abstinence motivation, opioid agonist effect rating, insomnia, and pain. Observation is continued for another 36 weeks in order to assess longer-term safety, adherence and effectiveness. The study is an investigator-initiated trial, funded by public grants and approved by an Independent Ethical Committee (the Regional Ethical Committee for Research South-East B # 2011/1320) and the Norwegian Medicines Agency. Despite minor implementation problems, the protocol appears sufficiently robust to generate results of high interest to

  1. Ethical and Clinical Safety Considerations in the Design of an Effectiveness Trial: A Comparison of Buprenorphine versus Naltrexone Treatment for Opioid Dependence

    Science.gov (United States)

    Nunes, Edward V.; Lee, Joshua D; Sisti, Dominic; Segal, Andrea; Caplan, Arthur; Fishman, Marc; Bailey, Genie; Brigham, Gregory; Novo, Patricia; Farkas, Sarah; Rotrosen, John

    2017-01-01

    We examine ethical challenges encountered in the design of an effectiveness trial (CTN-0051; X:BOT), comparing sublingual buprenorphine-naloxone (BUP-NX), an established treatment for opioid dependence, to the newer extended-release injectable naltrexone (XR-NTX). Ethical issues surrounded: 1) Known poor effectiveness of one possible, commonly used Treatment as Usual control condition—detoxification followed by counseling without medication; 2) The role of patients' preferences for treatments, given that treatments were clinically approved and available to the population; 3) Differences between the optimal “usual treatment” clinical settings for different treatments making it challenging to design a fair comparison; 4) Vested interest groups favoring different treatments exerting potential influence on the design process; 5) Potentially vulnerable populations of substance users and prisoners; 6) Potential therapeutic misconception in the implementation of safety procedures; and 7) High cost of a large trial limiting questions that could be addressed. We examine how the design features underlying these ethical issues are characteristic of effectiveness trials, which are often large trials that compare treatments with varying degrees of existing effectiveness data and familiarity to patients and clinicians, in community-based treatment settings, with minimal exclusion criteria that could involve vulnerable populations. Hence, investigators designing effectiveness trials may wish to remain alert to the possibility of similar ethical issues. PMID:27687743

  2. [National and regional market penetration rates of generic's high dosage buprenorphine: its evolution from 2006 to 2008, using reimbursed drug database].

    Science.gov (United States)

    Boczek, Christelle; Frauger, Elisabeth; Micallef, Joëlle; Allaria-Lapierre, Véronique; Reggio, Patrick; Sciortino, Vincent

    2012-01-01

    To assess the national market penetration rate (PR) of generic high-dosage buprenorphine (HDB) in 2008 and its evolution since their marketing (2006), and making a point for each dosage and at regional level. Retrospective study over data using national and regional health reimbursement database over three years (2006-2008). In 2008, the generic HDB's national MPR was 31%. The PR for each dosage were 45% for 0.4 mg, 36% for 2 mg and 19% for 8 mg. The (PR) based on Defined Daily Dose (DDD) was 23% in 2008, 15% in 2007 and 4% in 2006. In 2008, at the regional level, disparities were observed in the adjusted penetration rate from 15% in Île de France to 39% in Champagne Ardennes Lorraine. The national PR of generic HDB has increased. There are differences in MPR in terms of dosage and area. However, this PR is still low (in 2008, 82% of the delivered drugs are generics). © 2012 Société Française de Pharmacologie et de Thérapeutique.

  3. Comparison of abuse, suspected suicidal intent, and fatalities related to the 7-day buprenorphine transdermal patch versus other opioid analgesics in the National Poison Data System.

    Science.gov (United States)

    Coplan, Paul M; Sessler, Nelson E; Harikrishnan, Venkatesh; Singh, Richa; Perkel, Charles

    2017-01-01

    Prescription opioid related abuse, suicide and death are significant public health problems. This study compares rates of poison center calls categorized as intentional abuse, suspected suicidal intent or fatality for the 7-day buprenorphine transdermal system/patch (BTDS) with other extended-release and long-acting (ER/LA) opioids indicated for chronic pain. Retrospective 24-month cohort study using National Poison Data System data from July 2012 through June 2014. BTDS was introduced in the United States in January 2011. Numbers and rates of calls of intentional abuse, suspected suicidal intent and fatalities were evaluated for BTDS, ER morphine, ER oxycodone, fentanyl patch, ER oxymorphone and methadone tablets/capsules, using prescription adjustment to account for community availability. Rate ratios (RR) and 95% confidence intervals (CI) were calculated. Absolute numbers and prescription-adjusted rates of intentional abuse and suspected suicidal intent with BTDS were significantly lower (p opioid analgesics examined. No fatalities associated with BTDS exposure were reported. This post-marketing evaluation of BTDS indicates infrequent poison center calls for intentional abuse and suspected suicidal intent events, suggesting lower rates of these risks with BTDS compared to other ER/LA opioids.

  4. A case report on the treatment of complex chronic pain and opioid dependence by a multidisciplinary transitional pain service using the ACT Matrix and buprenorphine/naloxone

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    Weinrib AZ

    2017-03-01

    Full Text Available Aliza Z Weinrib,1,2 Lindsay C Burns,1,2 Alex Mu,1 Muhammad Abid Azam,1,2 Salima SJ Ladak,1 Karen McRae,1,3 Rita Katznelson,1,3 Saam Azargive,1 Cieran Tran,1 Joel Katz,1–3 Hance Clarke1,3 1Pain Research Unit, Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, 2Department of Psychology, York University, 3Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada Abstract: In an era of growing concern about opioid prescribing, the postsurgical period remains a critical window with the risk of significant opioid dose escalation, particularly in patients with a history of chronic pain and presurgical opioid use. The purpose of this case report is to describe the multidisciplinary care of a complex, postsurgical pain patient by an innovative transitional pain service (TPS. A 59-year-old male with complex chronic pain, as well as escalating long-term opioid use, presented with a bleeding duodenal ulcer requiring emergency surgery. After surgery, the TPS provided integrated pharmacological and behavioral treatment, including buprenorphine combined with naloxone and acceptance and commitment therapy (ACT using the ACT Matrix. The result was dramatic pain reduction and improved functioning and quality of life after 40+ years of chronic pain, thus changing the pain trajectory of a chronic, complex, opioid-dependent patient. Keywords: transitional pain service, postsurgical pain, chronic pain, opioid dependence, opioid weaning, acceptance and commitment therapy

  5. Efeitos antinociceptivos e sedativos da buprenorfina, da acepromazina ou da associação buprenorfina e acepromazina em gatos Antinociceptive and sedative effects of buprenorphine, acepromazine, or combination of both, in conscious cats

    Directory of Open Access Journals (Sweden)

    Luciana Alvarez Santana

    2010-10-01

    Full Text Available O efeito antinociceptivo da buprenorfina tem sido relatado em cães e gatos. No presente estudo, avaliou-se o limiar nociceptivo mecânico em felinos tratados com buprenorfina, acepromazina ou ambas associadas e foram comparados os efeitos antinociceptivos e sedativos da associação em relação ao uso isolado desses fármacos determinados pelo mesmo observador, por meio de analgesiômetro e da escala analógica visual dinâmica interativa (DIVAS, respectivamente. Os oito animais empregados no estudo foram previamente familiarizados com os procedimentos utilizados. Após quatro mensurações basais, foram administrados, por via intramuscular, 0,02mg kg-1 de buprenorfina, 0,06mg kg-1 de acepromazina ou 0,01mg kg-1 de buprenorfina associada a 0,03mg kg-1 de acepromazina, em um estudo cego, com delineamento em quadrado latino e tratamento semanal. Os efeitos antinociceptivos e sedativos foram avaliados aos 15, 30, 45 minutos e uma, duas, três, quatro, seis, oito e 12 horas após a administração do tratamento. O limiar nociceptivo mecânico se elevou significativamente apenas no grupo tratado com a associação buprenorfina-acepromazina (entre 45 minutos e uma hora. Em relação à sedação, nos grupos tratados com acepromazina e com a associação, os valores da DIVAS foram significativamente maiores, respectivamente, de 15 minutos até quatro horas e de 15 minutos até três horas pós-tratamento, não apresentando elevação desses valores com a buprenorfina. Concluiu-se que não foi possível verificar a superioridade da neuroleptoanalgesia em relação ao uso dos fármacos isoladamente.The antinociceptive effects of buprenorphine have been reported in dogs and cats. This study evaluated changes in the mechanical nociceptive threshold and the sedative effects of buprenorphine, acepromazine and its combination in cats, determined by the same observer using a nociceptive threshold testing device and DIVAS, respectively. Eight animals were

  6. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial.

    Science.gov (United States)

    Lee, Joshua D; Nunes, Edward V; Novo, Patricia; Bachrach, Ken; Bailey, Genie L; Bhatt, Snehal; Farkas, Sarah; Fishman, Marc; Gauthier, Phoebe; Hodgkins, Candace C; King, Jacquie; Lindblad, Robert; Liu, David; Matthews, Abigail G; May, Jeanine; Peavy, K Michelle; Ross, Stephen; Salazar, Dagmar; Schkolnik, Paul; Shmueli-Blumberg, Dikla; Stablein, Don; Subramaniam, Geetha; Rotrosen, John

    2018-01-27

    Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433. Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in

  7. Understanding abuse of buprenorphine/naloxone film versus tablet products using data from ASI-MV® substance use disorder treatment centers and RADARS® System Poison Centers.

    Science.gov (United States)

    Butler, Stephen F; Black, Ryan A; Severtson, Stevan Geoffrey; Dart, Richard C; Green, Jody L

    2018-01-01

    The objectives were to examine the abuse prevalence and route-of-administration (ROA) profiles of sublingual buprenorphine/naloxone combination (BNX) film in comparison with the BNX tablet and to identify clinically-relevant subgroups of patients or geographic patterns. Between Q1 2015 through Q3 2015, data were collected from two major surveillance systems: (1) assessment of individuals in substance use disorder (SUD) treatment collected from the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO®) ASI-MV® system and (2) intentional abuse/misuse exposures in the RADARS® System Poison Center Program. Poisson regression models were tailored to each system's data characteristics by population (all SUD treatment patients, US census) and adjusted for prescription volume. Effects of gender, race, age and US region as well as ROA profile were examined. For the ASI-MV study, 45,695 assessments of unique adults evaluated for substance use problems were collected. The abuse rate unadjusted for prescription volume of BNX tablet formulation was 2.64 cases/100 ASI-MV respondents versus 7.01 cases for the film formulation (RR=0.390, pfilm) (RR=1.25, pfilm abuse (0.0364) were greater than for tablet (0.0161), while prescription-adjusted rates were greater for tablet (0.2114) than for film (0.1703) per 100,000 prescriptions. ASI-MV ROA analyses indicated less abuse of the film by any alternate route, insufflation or injection than the tablet. Poison center data found more injection of tablets than film, although insufflation was not significantly different. On a prescription-adjusted basis, overall abuse of the BNX tablet is greater than that of the sublingual film formulation. For those who continue to abuse BNX, use by alternate ROAs was, in general, lower for the film. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Effects of premedication with sustained-release buprenorphine hydrochloride and anesthetic induction with ketamine hydrochloride or propofol in combination with diazepam on intraocular pressure in healthy sheep.

    Science.gov (United States)

    Gatson, Bonnie J; Pablo, Luisito; Plummer, Caryn E; Granone, Tiffany D

    2015-09-01

    To determine the effects of diazepam combined with ketamine hydrochloride or propofol for induction of anesthesia (IOA) following premedication with sustained-release buprenorphine hydrochloride (SRB) on intraocular pressure (IOP) in sheep. 20 healthy adult sheep. Diazepam with ketamine or propofol was given IV to each of 10 sheep after premedication with SRB (0.01 mg/kg, SC); after > 4 weeks, each sheep received the other induction combination with no premedication. For both eyes, IOPs were measured before premedication (if given), 10 minutes prior to (baseline) and immediately following administration of ketamine or propofol (time of IOA), after endotracheal intubation, and 5 minutes after IOA. Peak end-tidal P(CO2), globe position, and pupillary diameter were also analyzed. Data were not available for all sheep for all anesthetic episodes. Propofol-diazepam administration alone had no significant effect on IOP, whereas there was a significant decrease in IOP immediately following ketamine-diazepam administration alone. At 5 minutes after ketamine-diazepam administration, SRB-premedicated sheep had significantly higher IOP than unpremedicated sheep. Intraocular pressure was significantly higher at baseline, at intubation, and 5 minutes after IOA in SRB-premedicated sheep receiving propofol-diazepam, compared with unpremedicated sheep. Peak end-tidal P(CO2) at intubation was significantly higher in SRB-premedicated sheep. For sheep receiving either anesthetic treatment, IOPs did not differ significantly with or without SRB premedication. Globe position or pupillary diameter and IOP were not significantly related at any time point. Results suggested that both ketamine-diazepam and propofol-diazepam combinations were suitable for IOA without increasing IOP in sheep. The use of SRB should be avoided in sheep when increases in IOP are undesirable.

  9. Development and validation of a method for the determination of buprenorphine and norbuprenorphine in breast milk by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Nikolaou, Panagiota; Papoutsis, Ioannis; Athanaselis, Sotirios; Pistos, Constantinos; Dona, Artemis; Spiliopoulou, Chara

    2012-03-01

    Buprenorphine (BUP) is used for the maintenance of opioid-addicted pregnant women. Because BUP and its main metabolite nor-BUP are excreted into breast milk, a sensitive and specific GC/MS method has been developed, optimized and validated for their determination in breast milk. BUP-d4 was used as internal standard. The sample preparation includes combination of protein precipitation with solid-phase extraction and derivatization (acetylation). The absolute recovery for both analytes was found to be higher than 87.3%. The limits of detection and quantification were 0.07 and 0.20 µg/L, respectively. The calibration curves were linear within the dynamic range 0.20-20.0 µg/L, with a correlation coefficient higher than 0.996. Intra- and inter-day accuracies were ranged from -7.06 to 4.50 and from -5.88 to 7.00%, respectively, while intra- and inter-day precision were less than 5.7 and 6.1%. The analytes were found to be stable in breast milk at 4 °C for one week, at -20 °C for one month, and after three freeze-thaw cycles. The method can be used for the determination of BUP and nor-BUP in breast milk of BUP-maintained mothers, in order to calculate the amount of drug that could pass to the newborn via breast milk and to avoid toxic consequences of breastfeeding. Copyright © 2011 John Wiley & Sons, Ltd.

  10. A Subgroup Analysis Found no Diminished Response to Buprenorphine Transdermal System Treatment for Chronic Low Back Pain Patients Classified with Depression.

    Science.gov (United States)

    Yarlas, Aaron; Miller, Kate; Wen, Warren; Lynch, Shau Yu; Munera, Catherine; Dain, Bradley; Pergolizzi, Joseph V; Raffa, Robert; Ripa, Steven R

    2016-04-01

    Chronic pain (CP) patients with depression typically exhibit worse post-treatment outcomes than nondepressed CP patients. The cause is often assumed to reflect a differential response to treatment, neglecting other potential explanations, such as the continuation of differences in pretreatment outcomes. This post hoc analysis examines whether worse post-treatment outcomes for depressed patients with chronic low back pain (CLBP) are driven by reduced treatment efficacy. Data were from opioid-naïve adult patients with moderate-to-severe CLBP who participated in a randomized, placebo-controlled, double-blind clinical trial of Butrans(®) (buprenorphine) Transdermal System (BTDS) for pain relief. Depression screening was based on baseline SF-36v2 Mental Health subscale scores. Patient-reported measures of pain severity, pain interference, quality of life, sleep problems, and functional disability were administered at screening and during the study. Differential treatment efficacy for each outcome was examined using analysis of covariance models that included interaction terms between treatment arm and depression status. At baseline, patients classified as depressed showed greater pain interference, lower quality of life, more sleep problems, and greater functional disability than nondepressed patients; the two groups did not differ in pain severity. No statistically significant interactions between treatment arm and depression status were observed. The direction of improvement post-treatment favored the depressed group on nine of seventeen outcomes. Results do not support a differential response to BTDS treatment between depressed and nondepressed CLBP patients across a variety of patient-reported outcomes. These findings raise the question of whether depressed mood actually moderates the effectiveness of treatment in CP patients. © 2015 Optum. Pain Practice published by Wiley Periodicals, Inc. on behalf of World Institute of Pain.

  11. Poly-substance use and antisocial personality traits at admission predict cumulative retention in a buprenorphine programme with mandatory work and high compliance profile

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    Fridell Mats

    2011-05-01

    Full Text Available Abstract Background Continuous abstinence and retention in treatment for alcohol and drug use disorders are central challenges for the treatment providers. The literature has failed to show consistent, strong predictors of retention. Predictors and treatment structure may differ across treatment modalities. In this study the structure was reinforced by the addition of supervised urine samples three times a week and mandatory daily work/structured education activities as a prerequisite of inclusion in the program. Methods Of 128 patients consecutively admitted to buprenorphine maintenance treatment five patients dropped out within the first week. Of the remaining 123 demographic data and psychiatric assessment were used to predict involuntary discharge from treatment and corresponding cumulative abstinence probability. All subjects were administered the Structured Clinical Interview for DSM-IV-TR, and the Symptom Checklist 90 (SCL-90, the Alcohol Use Disorder Identification Test (AUDIT, the Swedish universities Scales of Personality (SSP and the Sense of Coherence Scale (SOC, all self-report measures. Some measures were repeated every third month in addition to interviews. Results Of 123 patients admitted, 86 (70% remained in treatment after six months and 61 (50% remained in treatment after 12 months. Of those discharged involuntarily, 34/62 individuals were readmitted after a suspension period of three months. Younger age at intake, poly-substance abuse at intake (number of drugs in urine, and number of conduct disorder criteria on the SCID Screen were independently associated with an increased risk of involuntary discharge. There were no significant differences between dropouts and completers on SCL-90, SSP, SOC or AUDIT. Conclusion Of the patients admitted to the programme 50% stayed for the first 12 months with continuous abstinence and daily work. Poly-substance use before intake into treatment, high levels of conduct disorder on SCID

  12. Satisfaction, Adherence and Health-Related Quality of Life with Transdermal Buprenorphine Compared with Oral Opioid Medications in the Usual Care of Osteoarthritis Pain.

    Science.gov (United States)

    Conaghan, Philip G; Serpell, Michael; McSkimming, Paula; Junor, Rod; Dickerson, Sara

    2016-08-01

    Osteoarthritis (OA) causes substantial pain and reduced health-related quality of life (HRQL). Although opioid analgesics are commonly used, the relative benefits of different opioids are poorly studied. Transdermal buprenorphine (TDB) offers an alternative to oral opioids for the treatment of moderate-to-severe chronic pain. This observational study of people with OA pain assessed satisfaction, HRQL and medication adherence. Patients in the UK with self-reported knee and/or hip OA who had been receiving one or more of TDB, co-codamol (an oral paracetamol/codeine combination) and tramadol for at least 1 month completed an online or telephone questionnaire. Medication satisfaction scores, HRQL scores (Short-Form 36 [SF-36]), medication adherence (Morisky Medication Adherence Scale [MMAS™]), adverse events and treatment discontinuations were recorded. Linear and logistic regression models were used to compare the treatment effect of TDB with co-codamol or tramadol. Overall, 966 patients met the inclusion criteria; 701 were taking only one of the target medications (TDB: 85; co-codamol: 373; tramadol: 243). The largest age group was 50-59 years and 76.0 % of patients were female. The TDB group was younger, with more male patients, therefore the statistical models were adjusted for age and sex. Medication satisfaction scores were significantly higher in the TDB group than the other two groups (TDB vs. co-codamol: 3.56, 95 % confidence interval [CI] 1.90-6.68, p pain treated with TDB were more satisfied and more adherent with their medication, and reported higher Physical Component Summary HRQL scores than those treated with co-codamol or tramadol, although demographic differences were observed between groups.

  13. Efficacy and tolerability of buccal buprenorphine in opioid-experienced patients with moderate to severe chronic low back pain: results of a phase 3, enriched enrollment, randomized withdrawal study

    Science.gov (United States)

    Gimbel, Joseph; Spierings, Egilius L.H.; Katz, Nathaniel; Xiang, Qinfang; Tzanis, Evan; Finn, Andrew

    2016-01-01

    Abstract A buccal film of buprenorphine (BBUP) was evaluated for safety and efficacy in a multicenter, double-blind, placebo-controlled, enriched-enrollment, randomized-withdrawal study in opioid-experienced patients (30 to ≤160 mg/d morphine sulfate equivalent) with moderate to severe chronic low back pain taking around-the-clock opioid analgesics. Patients' opioid doses were tapered to ≤30 mg morphine sulfate equivalent before open-label titration with BBUP (range, 150-900 μg every 12 hours). Patients who responded (received adequate analgesia that was generally well tolerated for 14 days) were randomized to receive buprenorphine (n = 254) or placebo (n = 257) buccal film. The primary efficacy variable was the change from baseline to week 12 of double-blind treatment in mean average daily pain-intensity scores using a rating scale of 0 (no pain) to 10 (worst pain imaginable). In the intent-to-treat population, mean pain scores were 6.7 after opioid taper and declined to 2.8 after the BBUP titration period. After randomization, mean pain scores were lower in the BBUP group than in the placebo group; the difference between groups in the mean change from baseline to week 12 was −0.98 (95% CI, −1.32 to −0.64; P pain reductions ≥30% and ≥50% (P low back pain. PMID:27434505

  14. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone).

    Science.gov (United States)

    Pergolizzi, Joseph; Böger, Rainer H; Budd, Keith; Dahan, Albert; Erdine, Serdar; Hans, Guy; Kress, Hans-Georg; Langford, Richard; Likar, Rudolf; Raffa, Robert B; Sacerdote, Paola

    2008-01-01

    SUMMARY OF CONSENSUS: 1. The use of opioids in cancer pain: The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities--including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia--and patient functional

  15. Subarachnoidally administered hyperbaric morphine, buprenorphine, methadone, and 10% dextrose on cardiopulmonary function and behavior in horses Administração subaraquenóide de morfina, buprenorfina, metadona hiperbáricos e dextrose 10% sobre as funções cardiopulmonar e comportamental em cavalos

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    Cláudio Corrêa Natalini

    2006-10-01

    Full Text Available The study was done to compare the heart rate, arterial blood pressure, arterial blood gases, respiratory rate, body temperature, and behavior after subarachnoid administration of hyperbaric morphine (MorphineD10, buprenorphine (BuprenorphineD10, methadone (Methadone D10, and 10% dextrose (D10 in conscious horses. Six adult horses were studied. Treatments were administered into the lombo-sacral subarachnoid space through an epidural catheter, MorphineD10 at 0.01mg kg-1, BuprenorphineD10 at 0.001mg kg-1, MethadoneD10 at 0.01mg kg-1, and 10% dextrose as a control group. The results showed that there are minimum changes in heart and respiratory rate, blood gases, blood pressure, and body temperature after subarachnoid administration of hyperbaric opioids in horses. No sedation and nor motor impairment or behavioral changes occur.O estudo foi realizado com a finalidade de comparar a freqüência cardíaca, a pressão sanguínea arterial, à análise de gases, a freqüência respiratória, a temperatura corpórea e o comportamento de eqüinos após a administração subaraquenóide de morfina hiperbárica (MorfinaD10, buprenorfina hiperbárica (BuprenorfinaD10, metadona hiperbárica (MetadonaD10 e dextrose 10% (D10. As doses de MorphinaD10 (0.01mg kg-1, BuprenorfinaD10 (0.001mg kg-1, MetadonaD10 (0.01mg kg-1 e dextrose 10% (grupo controle, 5ml foram administradas no espaço subaracnóide da região lombo-sacra de seis cavalos adultos, por meio de um catéter epidural. Os resultados mostraram alterações mínimas nas freqüências cardíaca e respiratória, na análise de gases, na pressão arterial e na temperatura corpórea após a administração subaracnóide de opióides hiperbáricos em cavalos. Os animais não apresentaram sedação, ataxia nem alteração comportamental.

  16. A novel form of dependency of hepatic extraction ratio of opioids in vivo upon the portal vein concentration of drug: comparison of morphine, diamorphine, fentanyl, methadone and buprenorphine in the chronically cannulated cow.

    Science.gov (United States)

    Bullingham, R E; Moore, R A; Symonds, H W; Allen, M C; Baldwin, D; McQuay, H J

    1984-05-21

    In the chronically cannulated cow, the hepatic extraction ratio for intravenous boluses of morphine, diamorphine, fentanyl, methadone and buprenorphine increased towards a plateau value as portal vein drug concentration increased. An extraction ratio close to zero for morphine was observed at a portal vein plasma drug concentration of about 200 nanomol per litre, which is within the range for significant pharmacodynamic effects. The similar concentrations extrapolated for the other narcotics would be of less pharmacodynamic importance. The phenomenon did not depend with morphine on the history of drug delivery to the liver; measurement of hepatic blood flow showed the effect was not an artifact of unrepresentative blood sampling, and was not related to any action of the narcotics on hepatic blood flow. The existence of this novel type of concentration dependent hepatic extraction ratio in vivo can explain a number of anomalous observations on narcotic pharmacokinetics, especially for morphine. Furthermore, similar behaviour may be expected for non-opioid drugs having similar pharmacokinetic properties.

  17. Management of opioid-dependent patients: comparison of the cost associated with use of buprenorphine/naloxone or methadone, and their interactions with concomitant treatments for infectious or psychiatric comorbidities.

    Science.gov (United States)

    Roncero, Carlos; Domínguez-Hernández, Raquel; Díaz, Tomás; Fernández, José Manuel; Forcada, Rafael; Martínez, José Manuel; Seijo, Pedro; Terán, Antonio; Oyagüez, Itziar

    2015-09-15

    The objective was to estimate the annual interaction management cost of agonist opioid treatment (AOT) for opioid-dependent (OD) patients with buprenorphine-naloxone (Suboxone®) (B/N) or methadone associated with concomitant treatments for infectious (HIV) or psychiatric comorbidities. A costs analysis model was developed to calculate the associated cost of AOT and interaction management. The AOT cost included pharmaceutical costs, drug preparation, distribution and dispensing, based on intake regimen (healthcare center or take-home) and type and frequency of dispensing (healthcare center or pharmacy), and medical visits. The cost of methadone also included single-dose bottles, monthly costs of custody at pharmacy, urine toxicology drug screenings and nursing visits. Potential interactions between AOT and concomitant treatments (antivirals, antibacterials/antifungals, antipsychotics, anxiolytics, antidepressant and anticonvulsants), were identified to determine the additional use of healthcare resources for each interaction management. The annual cost per patient of AOT was €1,525.97 for B/N and €1,467.29 for methadone. The average annual cost per patient of interaction management was €257.07 (infectious comorbidities), €114.03 (psychiatric comorbidities) and €185.55 (double comorbidity) with methadone and €7.90 with B/N in psychiatric comorbidities. Total annual costs of B/N were €1,525.97, €1,533.87 and €1,533.87 compared to €1,724.35, €1,581.32 and €1,652.84 for methadone per patient with infectious, psychiatric or double comorbidity respectively.Compared to methadone, the total cost per patient with OD was lower with B/N (€47.45-€198.38 per year). This is due to the differences in interaction management costs associated with the concomitant treatment of infectious and/or psychiatric comorbidities.

  18. Efeitos cardiovasculares e neuroendócrinos do butorfanol e da buprenorfina em cães anestesiados pelo desfluorano Cardiovascular and neuroendocrine effects of butorphanol and buprenorphine in dogs anesthetized with desflurane

    Directory of Open Access Journals (Sweden)

    A.P. Souza

    2007-04-01

    Full Text Available Avaliaram-se os efeitos do butorfanol e da buprenorfina sobre variáveis cardiovasculares e neuroendócrinas em cães anestesiados com desfluorano, utilizando-se 30 cães adultos, machos e fêmeas, distribuídos em três grupos denominados grupo butorfanol (GBT, grupo buprenorfina (GBP e grupo-controle (GCO. A anestesia foi induzida com propofol (8mg/kgIV e nos animais intubados administrou-se desfluorano (1,5CAM. Após 30 minutos, nos cães do GBT, aplicou-se butorfanol (0,4mg/kgIM; nos do GBP, buprenorfina (0,02mg/kgIM; e nos do GCO, solução de NaCl a 0,9% (0,05ml/kgIM. Avaliaram-se: freqüência cardíaca; pressões arteriais sistólica, diastólica e média; débito cardíaco; pressão venosa central; cortisol; hormônio adrenocorticotrópico; noradrenalina; e glicose. As colheitas dos dados foram feitas aos 30 minutos após o início da administração do desfluorano (M0, 15 minutos após a administração do opióide ou placebo (M15, e a cada 15 minutos após M15 (M30, M45, M60 e M75. Para a avaliação neuroendócrina utilizaram-se os momentos M-30 (antes da administração dos fármacos, M0, M15 e M45. Na freqüência cardíaca houve diferença entre M0 e M15 (129 e 111bat/min em GBT, e entre M0 e M30 (131 e 112bat/min em GBP. Na pressão arterial média, a diferença foi entre M0 (86mmHg e todos os momentos que se seguiram (todos os valores foram menores que 72mmHg, em GBT. A pressão arterial diastólica foi menor em todos os momentos (The effects of butorphanol and buprenorphine on cardiovascular and neuroendocrine variables in dogs anesthetized with desflurane were studied. Thirty adult healthy, males and females, mongrel dogs were distributed in three groups denominated butorphanol group (BTG, buprenorphine group (BPG and control group (COG. The anesthetic induction was done using propofol (8mg/kg, IV, and immediately, the dogs were intubated and submited to desflurane anaesthesia (1.5 MAC. After 30 minutes, the BTG animals

  19. Buprenorphine Sublingual and Buccal (opioid dependence)

    Science.gov (United States)

    ... and naloxone are used to treat opioid dependence (addiction to opioid drugs, including heroin and narcotic painkillers). ... are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking or using ...

  20. Facts about Buprenorphine for Treatment of Opioid Addiction

    Science.gov (United States)

    ... streets, I’d been in detox. It was jails, institutions …. Death, I knew, was imminent for me … ... WayS To ReduCe TheM Body aches, headaches,and cold-or flu- like symptoms — Check with your doctor ...

  1. Continuous infusion in adult females dogs submitted to ovariohysterectomy with midazolam-xylazine and/or medetomidine pre-treated with methotrimeprazine and buprenorphine Infusão continua em cães fêmeas submetidas à ovariohisterectomia com midazolam/cetamina/xilazina e/ou medetomidina pré-tratadas com levomepromazina e buprenorfina

    Directory of Open Access Journals (Sweden)

    Fernando do Carmo Silva

    2007-08-01

    Full Text Available PURPOSE: To compare, by continuous infusion of ketamine or medetomidine combined to methotrimeprazine and buprenorphine, ketamine and midazolam, the degree of hypnosis, myorelaxation, anesthetic quality and surgical feasibility through evaluation of possible parametric alterations and recovery quality. METHODS: 20 healthy adult females dogs, aged 3 to 5 years, body weight between 7 and 15 kg, were assigned randomly and homogenously to 2 groups of 10 animals each (n=10, group 1 (G1 and group 2 (G2, respectively. Animals of G1 were subjected to a pre-treatment with intravenous 1.0 mg/kg methotrimeprazine and or 3ì/kg. After 15 minutes, a 5.0 mg/kg ketamine and 0.2 mg/kg midazolam were intravenously injected. Immediately after induction, an anesthetic combination of 0.4 mg/kg/h midazolam, 20 mg/kg/h ketamine and 1.0 mg/kg/h xylazine, was continuously and intravenously administered for 30 minutes. The same techniques were used in G2 except for the substitution of xylazine for 30ìg/kg/h medetomidine. RESULTS: In G1 there was a 1st and 2nd degree atrioventricular heart block, a longer recovery period and lower quality. In G2 a 1st degree atrioventricular heart block occurred but isolated and ephemeral. CONCLUSIONS: The continuous infusion method, besides reducing drugs utilization, prevented collateral effects allowing a more tranquil recovery with no excitations, both protocols permitted the surgical procedure (ovary-hysterectomy bringing about a reduction in hypnosis and an accentuated myorelaxation. Xylazine and medetomidine showed a similar pharmacodynamic behavior but with different clinical aspects. The electrocardiographic alterations observed in G2 and in a lower degree in G1 must be well studied. Describers: dogs, ketamine, methotrimeprazine, medetomidine, midazolam and xylazine.OBJETIVO: Comparar através de infusão contínua de xilazina ou medetomidina associada à metotrimeprazina e buprenorfina, cetamina e midazolam, o grau de hipnose

  2. Avaliação algimétrica por estímulo nociceptivo térmico e pressórico em cães pré-tratados com levomepromazina, midazolam e quetamina associados ou não ao butorfanol ou buprenorfina The algimetry evaluation for thermic and pressoric nociceptive stimulus in pre treated dogs with methotrimeprazine, midazolam and ketamine associated or not with butorphanol or buprenorphine

    Directory of Open Access Journals (Sweden)

    André Leguthe Rosa

    2005-02-01

    methotrimeprazine and midazolam put on the same syringe with ketamine. The animals of GII received the same treatment of GI but associated with butorphanol and finally the animals of GIII received the same treatment of GI but associated with buprenorphine. The routine parametric evaluations has been proceeded, although using the thermo algimetry measured in °C with the average of 52°C and the pressoric algimetry in Kg. RESULTS: In the thermo algimetry, there has been significant difference in GI at the moments M0, M1, M4 and M5; in GII it was found at M0, M1, M5 and M6 and in GIII it was observed the significant at M0 and M1. It has also been shown in pressoric algimetry significant difference in GI at the moments M0, M2 and M3. Among GII it has observed significant difference at all moments and it has found at M0, M9 in GIII. Thus, it has observed significant differences between all groups; for such the M2 of GII smaller than the others; and M4, M5 of GIII bigger than GI and GII. In the assessment of all periods it was observed significant latent period bigger in GI, however, with reasonable period and short recovery in GII and GIII. In the order hand, the postural tonus recovery it was longer in GIII, followed by GII and finally GI. CONCLUSION: The used method for the measurement of algic stimulus was efficient, noticing a reasonable analgesic period of 3 hours for butorphanol and 6 hours for buprenorphine.

  3. Drug: D10250 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10250 Mixture, Drug Buprenorphine - naloxone mixt; Suboxone (TN) (Buprenorphine hy...DDICTIVE DISORDERS N07BC Drugs used in opioid dependence N07BC51 Buprenorphine, combinations D10250 Buprenorphine - naloxone...pioid Dependence Treatments Buprenorphine/Naloxone D10250 Buprenorphine - naloxone mixt PubChem: 163312281 ...

  4. Patterns in sleep-wakefulness in three-month old infants exposed to methadone or buprenorphine.

    Science.gov (United States)

    Sarfi, Monica; Martinsen, Harald; Bakstad, Brittelise; Røislien, Jo; Waal, Helge

    2009-12-01

    Infants exposed to opioides in-utero frequently demonstrate withdrawal symptoms in the neonatal period and have difficulties with state regulation. This study examines sleep-wakefulness-distress patterns as indicators of regulatory mechanisms at 3 months of age. A national infant cohort (N=35) born to women in high-dose maintenance treatment during pregnancy and a comparison group (N=36) of low-risk infants born in the same period. Distributions and frequencies of sleep, wakefulness and distress measured in hours and episodes on sleep charts recorded by the mothers in the two groups. Women in maintenance treatment were monitored closely during pregnancy to avoid illicit drug use and to be prepared for motherhood. They were also offered residential treatment before pregnancy and after the child was born. There were no statistical differences between the two groups in any of the 10 measures reflecting diurnal and nocturnal rhythmicity at 3 months despite of neonatal abstinence syndrome in 47% of the exposed infants and significant differences in infant characteristics with respect to birth weight, gestational age and maternal characteristics. Follow-up procedures combining drug monitoring and counseling during pregnancy and in the first months after birth enhance the development of state regulation in terms of sleep-wakefulness patterns.

  5. Improved memory for reward cues following acute buprenorphine administration in humans

    NARCIS (Netherlands)

    Syal, Supriya; Ipser, Jonathan; Terburg, David; Solms, Mark; Panksepp, Jaak; Malcolm-Smith, Susan; Bos, Peter A.; Montoya, Estrella R.; Stein, Dan J.; van Honk, Jack

    2015-01-01

    In rodents, there is abundant evidence for the involvement of the opioid system in the processing of reward cues, but this system has remained understudied in humans. In humans, the happy facial expression is a pivotal reward cue. Happy facial expressions activate the brain's reward system and are

  6. Use of Buprenorphine in Children With Chronic Pseudoobstruction Syndrome Case Series and Review of Literature

    NARCIS (Netherlands)

    Prapaitrakool, Sunisa; Hollmann, Markus W.; Wartenberg, Hans Christian; Preckel, Benedikt; Brugger, Stefan

    2012-01-01

    Objectives: Abdominal pain is the most challenging symptom in chronic intestinal pseudoobstruction (CIPO) syndrome, because of its severity and the limited availability of suitable opioid formulations, especially in pediatric patients with digestive problems. Most of the children with CIPO cannot

  7. Screening for drugs of abuse (II): Cannabinoids, lysergic acid diethylamide, buprenorphine, methadone, barbiturates, benzodiazepines and other drugs.

    Science.gov (United States)

    Simpson, D; Braithwaite, R A; Jarvie, D R; Stewart, M J; Walker, S; Watson, I W; Widdop, B

    1997-09-01

    Requirements for the provision of an efficient and reliable service for drugs of abuse screening in urine have been summarized in Part I of this review. The requirements included rapid turn-around times, good communications between requesting clinicians and the laboratory, and participation in quality assessment schemes. In addition, the need for checking/confirmation of positive results obtained for preliminary screening methods was stressed. This aspect of the service has assumed even greater importance with widespread use of dip-stick technology and the increasing number of reasons for which drug screening is performed. Many of these additional uses of drug screening have possible serious legal implications, for example, screening school pupils, professional footballers, parents involved in child custody cases, persons applying for renewal of a driving licence after disqualification for a drug-related offence, doctors seeking re-registration after removal for drug abuse, and checking for compliance with terms of probation orders; as well as pre-employment screening and work-place testing. In many cases these requests will be received from a general practitioner or drug clinic with no indication of the reason for which testing has been requested. This also raises the serious problems of a chain of custody, provision of two samples, stability of samples, and secure and lengthy storage of samples in the laboratory-samples may be requested by legal authorities several months after the initial testing. The need for confirmation of positive results is now widely accepted but it may be equally important to confirm unexpected negative results. Failure to detect the presence of maintenance drugs may lead to the patient being discharged from a drug treatment clinic and, if attendance at the clinic is one of the terms of continued employment, to dismissal. It seems likely that increasing abuse of drugs and the efforts of regulatory authorities to control this, will lead to the manufacture of more designer drugs. Production of substituted phenethylamines was facilitated by the drug makers' cook book, 'PIHKAL' (Phenethylamines I Have Known And Loved) by Dr Alexander Shulgin and Ann Shulgin, and production of substituted tryptamines is promised in their next book, TIHKAL. Looking to the future, laboratories will need to ensure that they can detect and quantitate an ever-increasing number of drugs and related substances. The question of confidence in results of drugs of abuse testing raised in 1993 by Watson has assumed even greater importance as a result of attention focused on the OJ Simpson trial in Los Angeles. Toxicological investigations are likely to be challenged more frequently in the future. Even if analyses have been performed by GC-MS, there is a need to establish the level of match between the spectrum of the unknown substance and a library spectrum which is considered acceptable for legal purposes. It will also be essential to ensure that computer libraries contain spectra for all substances likely to be encountered in drugs of abuse screening.

  8. Behavioural Outcomes of Four-Year-Old Children Prenatally Exposed to Methadone or Buprenorphine: A Test of Three Risk Models

    Science.gov (United States)

    Konijnenberg, Carolien; Lund, Ingunn Olea; Melinder, Annika

    2015-01-01

    It is still under debate whether the reported effects of opioid maintenance therapy (OMT) on child behaviour are a direct effect of prenatal exposure, or whether other factors are involved. This prospective cohort study investigated three models: the teratogenic risk model, the maternal risk model, and a combined risk model in a group of 35…

  9. 77 FR 72752 - Opioid Drugs in Maintenance and Detoxification Treatment of Opiate Addiction; Proposed...

    Science.gov (United States)

    2012-12-06

    ...-supported network of Addiction Technology Transfer Centers (ATTCs) offers classroom training and other... Opiate Addiction; Proposed Modification of Dispensing Restrictions for Buprenorphine and Buprenorphine... responsibility and stability to receive opioid addiction treatment medication. Opioid treatment programs that use...

  10. Dgroup: DG01717 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG01717 DGroup Drugs for opioid dependence ... DG00820 ... Buprenorphine ... D07132 ... Bupre...norphine (JAN/INN) ... D00836 ... Buprenorphine hydrochloride (JP17/USP) ... DG00999 ... Methadone ... D08195 ... Methado... Naloxone ... D08249 ... Naloxone (INN) ... D01340 ... Naloxone hydrochloride (JP17/USP) ... Other ... DG01718 ... Drugs for addictive disorder ATC code: N07BC Drugs of addictive disorder ...

  11. Poly-substance use and antisocial personality traits at admission predict cumulative retention in a buprenorphine programme with mandatory work and high compliance profile

    DEFF Research Database (Denmark)

    Öhlin, Leif; Hesse, Morten; Fridell, Mats

    2011-01-01

    -IV-TR, and the Symptoms Checklist 90 (SCL-90), the Alcohol Use Disorder Identification Test (AUDIT), the Swedish universities Scales of Personality (SSP) and the Sense of Coherence Scale (SOC), all self-report measures. Some measures were repeated every third month in addition to interviews. Results Of 123 patients......Background Continuous abstinence and retention in treatment for alcohol and drug use disorders are central challenges for the treatment providers. The literature has failed to show consistent, strong predictors of retention. Predictors and treatment structure may differ across treatment modalities......), and number of conduct disorder criteria on the SCID Screen were independently associated with an increased risk of involuntary discharge. There were no significant differences between dropouts and completers on SCL-90, SSP, SOC or AUDIT. Conclusion Of the patients admitted to the programme 50% stayed...

  12. Consumer attitudes about opioid addiction treatment: a focus group study in New York City.

    Science.gov (United States)

    Sohler, Nancy L; Weiss, Linda; Egan, James E; López, Carolina M; Favaro, Jamie; Cordero, Robert; Cunningham, Chinazo O

    2013-01-01

    To develop effective programs for people who are opioid dependent and to impact the opioid epidemic in New York City, it is crucial to monitor attitudes about opioid addiction treatments among opioid users who have experienced barriers to engagement and retention in addiction treatment. The authors conducted a qualitative study using focus groups. Six focus groups in three needle exchanges in New York City were audio recorded, transcribed, and systematically coded. The authors report on the main themes related to the study objectives. Participants of each needle exchange who were opioid dependent and had some knowledge of both methadone and buprenorphine were eligible. There were four main findings. Participants felt the following: 1) buprenorphine is an appropriate option for those heroin users who are motivated to stop using, 2) they have less control over their addiction treatment with methadone than they would have with buprenorphine, 3) buprenorphine treatment is not accessible to many New York City residents who would benefit from this treatment, and 4) lack of access to buprenorphine treatment is a cause of treatment-related diversion. Both methadone maintenance and buprenorphine treatment opportunities are necessary to address the diverse treatment needs of opioid-dependent people in New York City. However, the current medical model of buprenorphine treatment may be too restrictive for some opioid-dependent people and may be contributing to the use of illicit buprenorphine. New models to deliver buprenorphine treatment may address these problems.

  13. CDC Vital Signs: Opioid Painkiller Prescribing

    Science.gov (United States)

    ... Health Services Administration Medication-Assisted Treatment for Opioid Addiction: Facts for Families and Friends Opioid Overdose Prevention Toolkit Buprenorphine Treatment Locator Mental Health Treatment Locator ...

  14. Defeating the dragon.indd

    African Journals Online (AJOL)

    South Africa is situated along one of the primary drug trafficking routes through ... of patients presenting for substance treatment who report heroin as their .... Buprenorphine-naloxone combination. Initial reports suggested that buprenorphine would have low abuse potential.28. However, parenteral abuse and black-market.

  15. Department of Health and Human Services Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-12-20

    ... regulations. It will modify the dispensing requirements for buprenorphine and buprenorphine combination...), USDA/CVB (Center for Veterinary Biologics), and the Department of Defense (DOD)/United States Army... Veterinary Medicine, Room 101, (MPN-4, HFV-232), 7519 Standish Place, Rockville, MD 20855 Phone: 240 276-9242...

  16. New developments in the management of opioid dependence: focus on sublingual buprenorphine–naloxone

    Directory of Open Access Journals (Sweden)

    Soyka M

    2015-01-01

    Full Text Available Michael Soyka1,21Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität, Munich, Germany; 2Private Hospital Meiringen, Meiringen, SwitzerlandAbstract: Opioid maintenance therapy is a well-established first-line treatment approach in opioid dependence. Buprenorphine, a partial opioid agonist, has been found by numerous studies to be an effective and safe medication in the treatment of opioid dependence. At present, buprenorphine is available as a monodrug or in a fixed 4:1 ratio combination with naloxone. A diminished risk of diversion and abuse for the buprenorphine–naloxone combination is likely but not firmly established. Conventional formulations are given sublingually to avoid the hepatic first-pass effect. A novel film tablet is available only in the US and Australia. Other novel, sustained-release formulations (implant, depot are currently being developed and tested. Recent studies, including a Cochrane meta-analysis, suggest that the retention with buprenorphine is lower than for methadone, but that buprenorphine may be associated with less drug use. Higher doses of buprenorphine are associated with better retention rates. Buprenorphine has a ceiling effect at the opioid receptor with regard to respiratory depression, and may cause fewer fatal intoxications than methadone. Possible antidepressant effects of buprenorphine and its use in comorbid psychiatric patients has not been studied in much detail. Clinical implications are discussed.Keywords: buprenorphine, methadone, naloxone, opioids, opioid dependence, therapy

  17. Agonist-selective effects of opioid receptor ligands on cytosolic calcium concentration in rat striatal neurons.

    Science.gov (United States)

    Brailoiu, G Cristina; Deliu, Elena; Hooper, Robert; Dun, Nae J; Undieh, Ashiwel S; Adler, Martin W; Benamar, Khalid; Brailoiu, Eugen

    2012-06-01

    Buprenorphine is an opioid receptor ligand whose mechanism of action is incompletely understood. Using Ca(2+) imaging, we assessed the effects of buprenorphine, β-endorphin, and morphine on cytosolic Ca(2+) concentration [Ca(2+)](i), in rat striatal neurons. Buprenorphine (0.01-1 μM) increased [Ca(2+)](i) in a dose-dependent manner in a subpopulation of rat striatal neurons. The effect of buprenorphine was largely reduced by naloxone, a non-selective opioid receptor antagonist, but not by μ, κ, δ or NOP-selective antagonists. β-Endorphin (0.1 μM) increased [Ca(2+)](i) with a lower amplitude and slower time course than buprenorphine. Similar to buprenorphine, the effect of β-endorphin was markedly decreased by naloxone, but not by opioid-selective antagonists. Morphine (0.1-10 μM), did not affect [Ca(2+)](i) in striatal neurons. Our results suggest that buprenorphine and β-endorphin act on a distinct type/subtype of plasmalemmal opioid receptors or activate intracellular opioid-like receptor(s) in rat striatal neurons. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  18. Impact of Opioid and Nonopioid Drugs on Postsurgical Pain Management in the Rat

    Directory of Open Access Journals (Sweden)

    Natalie M. Wilson

    2016-01-01

    Full Text Available Aim. Nonsteroidal anti-inflammatory drugs or opioids are commonly used to control surgical pain following veterinary and clinical procedures. This study evaluated the efficacy of postoperative ketorolac or buprenorphine following abdominal surgery. Main Methods. Mean arterial pressure (MAP, heart rate, animal activity, corticosterone levels, and a nociceptive sensitivity assay were used to evaluate 18 adult male Sprague-Dawley rats which underwent aortic artery occlusion for implantation of a radiotelemetry device. The animals were treated postoperatively with intraperitoneal injections of vehicle, ketorolac (10 mg/kg, or buprenorphine (0.06 mg/kg every 8 hours for 3 days. Key Findings. There were no consistent significant changes in any of the telemetry parameters after treatment with ketorolac compared with no saline treatment with the exception of increased MAP in the buprenorphine group during the first 48 hours when compared with other treatment groups. There was a sustained increase in fecal corticosterone levels from baseline on days 2–7 with buprenorphine compared with vehicle- or ketorolac-treated animals. All treatment conditions displayed reduced paw withdrawal thresholds (PWTs from day 1 to day 21 following surgery. Compared with the vehicle treatment group, buprenorphine-treated animals exhibited significantly lower PWT levels from day 4 to 14 days. Significance. Given the prolonged increase in fecal corticosterone levels and pronounced changes in tactile hyperalgesia behavior in rodents subjected to buprenorphine treatment, these data suggest that ketorolac may be superior to buprenorphine for the treatment of postprocedure pain behavior in rodents.

  19. Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen

    DEFF Research Database (Denmark)

    Fanoe, Søren; Hvidt, C; Ege, P

    2007-01-01

    were collected in a population of adult heroin addicts treated with methadone or buprenorphine on a daily basis. Of the patients at the Drug Addiction Service in the municipal of Copenhagen, 450 ( 52%) were included. The QT interval was estimated from 12 lead ECGs. All participants were interviewed.......002). No association between buprenorphine and QTc was found. Among the subjects treated with methadone, 28% men and 32% women had prolonged QTc interval. None of the subjects treated with buprenorphine had QTc interval >0.440s . A 50 mg higher methadone dose was associated with a 1.2 (95% CI 1.1 to 1.4) times higher...

  20. Medications to Treat Opioid Addiction: Methadone

    Science.gov (United States)

    ... Updated: 09/28/2015 Medications to Treat OPIOID ADDICTION Methadone Naltrexone Buprenorphine Related SAMHSA Resources Behavioral Health ... Systems Integration Health Disparities Health Financing Health Information Technology HIV, AIDS, and Viral Hepatitis Homelessness and Housing ...

  1. Medication for Opioid Overdose: Naloxone

    Science.gov (United States)

    ... Updated: 03/03/2016 Medications to Treat OPIOID ADDICTION Methadone Naltrexone Buprenorphine Related SAMHSA Resources Behavioral Health ... Systems Integration Health Disparities Health Financing Health Information Technology HIV, AIDS, and Viral Hepatitis Homelessness and Housing ...

  2. Addiction Drug Underused by Primary Care Docs in U.S.

    Science.gov (United States)

    ... news/fullstory_167585.html Addiction Drug Underused by Primary Care Docs in U.S. Buprenorphine is prescribed to get ... opioid use disorder that's approved for prescription by primary care physicians, allowing treatment in the privacy of a ...

  3. Fact Sheets

    Science.gov (United States)

    ... PDF | Espanol PDF Bisphosphonate treatment PDF | Espanol PDF Buprenorphine PDF | Espanol PDF Bupropion (Wellbutrin®) PDF | Espanol PDF ... PDF | Espanol PDF Working as a Veterinarian or Veterinary Technician PDF | Espanol PDF Working in a Nail ...

  4. Index to Drug-Specific Information

    Science.gov (United States)

    ... Botulinium Type A and B Brentuximab vedotin Budesonide Buprenorphine Bupivicaine Bupropion Butisol sodium Bydureon (exenatide) Byetta (exenatide) ... Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products

  5. Opioid Overdose Prevention: Safety Advice for Patients & Family Members

    Science.gov (United States)

    ..