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Sample records for sublingual buprenorphine tablets

  1. 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...

  2. 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.

  3. 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

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

    Science.gov (United States)

    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

  5. 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

  6. 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...

  7. 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.

  8. 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

  9. 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

  10. 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

  11. Formulation and evaluation of sublingual tablets of losartan potassium

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    Nikunj J. Aghera

    2012-05-01

    Full Text Available Objective: Sublingual tablets of Losartan Potassium were prepared to improve its bioavailability, to avoid pre-systemic metabolism in the gastrointestinal tract and hepatic first pass elimination. Methods: The Sublingual tablets were prepared by direct compression procedure using different concentration of Starch 1500 and microcrystalline cellulose. Compatibility studies of drug and polymer were performed by FTIR spectroscopy and DSC. Preformulation property of API was evaluated. Postcompressional parameters such disintegration time, wetting time, water absorption ratio, in vitro drug release and in vivo bioavailability study of optimized formulation were determined. Results: FTIR spectroscopy and DSC study revealed that there was no possible interaction between drug and polymers. The precompression parameters were in acceptable range of pharmacopoeial specification. The disintegration time of optimized formulation (F3 was upto 48 sec. The in vitro release of Losartan Potassium was upto 15 min. The percentage relative bioavailability of Losartan Potassium from optimized sublingual tablets was found to be 144.7 %. Conclusions: Sublingual tablets of Losartan Potassium were successfully prepared with improved bioavailability.

  12. Fast-disintegrating sublingual tablets: Effect of epinephrine load on tablet characteristics

    OpenAIRE

    Rawas-Qalaji, Mutasem M.; Estelle, F.; Simons, R.; Simons, Keith J.

    2006-01-01

    The aim of this study was to evaluate the effect of increasing epinephrine load on the characteristics of fast-disintegrating sublingual tablets for the potential emergency treatment of anaphylaxis. Four tablet formulations, A, B, C, and D, containing 0%, 6%, 12%, and 24% of epinephrine bitartrate, respectively, and microcrystalline cellulose:low-substituted hydroxypropyl cellulose (9∶1), were prepared by direct compression, at a range of compression forces. Tablet weight variation, content u...

  13. 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.

  14. 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

  15. Clinical benefits of treatment with SQ house dust mite sublingual tablet in house dust mite allergic rhinitis.

    Science.gov (United States)

    Demoly, P; Kleine-Tebbe, J; Rehm, D

    2017-10-01

    Treatment with SQ (standardised quality) house dust mite sublingual tablet for 1 year resulted in a decreased probability of having an allergic rhinitis (AR) exacerbation day (from 11% [placebo] to 5% [SQ house dust mite sublingual tablet]) and an increased probability of having a mild AR day (from 16% [placebo] to 34% [SQ house dust mite sublingual tablet]). © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  16. Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma

    DEFF Research Database (Denmark)

    Virchow, Johann Christian; Backer, Vibeke; Kuna, Piotr

    2016-01-01

    IMPORTANCE: The house dust mite (HDM) sublingual allergen immunotherapy (SLIT) tablet is a potential novel treatment option for HDM allergy-related asthma. OBJECTIVES: To evaluate the efficacy and adverse events of the HDM SLIT tablet vs placebo for asthma exacerbations during an inhaled corticos...

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

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    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

  18. 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

  19. 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.

  20. Preparation and physicochemical evaluation of a new tacrolimus tablet formulation for sublingual administration

    NARCIS (Netherlands)

    Srinarong, Parinda; Pham, Bao T; Holen, Maru; van der Plas, Afke; Schellekens, Reinout C A; Hinrichs, Wouter L J; Frijlink, Henderik W

    The aim of this study was to develop a new fast-disintegrating tablet formulation containing 1mg tacrolimus for sublingual application. First, solid dispersions containing tacrolimus (2.5%, 5% and 10% w/w) incorporated in Ac-Di-Sol®and carriers (inulin 1.8kDa and 4kDa, and polyvinylpyrrolidone (PVP)

  1. Formulation and Evaluation of New Glimepiride Sublingual Tablets

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    Wafa Al-Madhagi

    2017-01-01

    Full Text Available Oral mucosal delivery of drugs promotes rapid absorption and high bioavailability, with a subsequent immediate onset of pharmacological effect. However, many oral mucosal deliveries are compromised by the possibility of the patient swallowing the active substance before it has been released and absorbed locally into the systemic circulation. The aim of this research was to introduce a new glimepiride formula for sublingual administration and rapid drug absorption that can be used in an emergency. The new sublingual formulation was prepared after five trials to prepare the suitable formulation. Two accepted formulations of the new sublingual product were prepared, but one of them with disintegration time of 1.45 min and searching for preferred formulation, the binder, is changed with Flulac and starch slurry to prepare formula with disintegration time of 21 seconds that supports the aim of research to be used in an emergency. The five formulations were done, after adjusting to the binder as Flulac and aerosil with disintegration time of 21 seconds and accepted hardness as well as the weight variation. The assay of a new product (subglimepiride is 103% which is a promising result, confirming that the formula succeeded. The new product (subglimepiride is accepted in most quality control tests and it is ready for marketing.

  2. Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation.

    Science.gov (United States)

    Ohashi-Doi, Katsuyo; Kito, Hirokazu; Du, Weibin; Nakazawa, Hiroshi; Ipsen, Henrik; Gudmann, Pernille; Lund, Kaare

    2017-01-01

    In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time. © 2017 S. Karger AG, Basel.

  3. 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.

  4. 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.

  5. Adrenaline (epinephrine) microcrystal sublingual tablet formulation: enhanced absorption in a preclinical model.

    Science.gov (United States)

    Rawas-Qalaji, Mutasem; Rachid, Ousama; Mendez, Belacryst A; Losada, Annette; Simons, F Estelle R; Simons, Keith J

    2015-01-01

    For anaphylaxis treatment in community settings, adrenaline (epinephrine) administration using an auto-injector in the thigh is universally recommended. Despite this, many people at risk of anaphylaxis in community settings do not carry their prescribed auto-injectors consistently and hesitate to use them when anaphylaxis occurs.The objective of this research was to study the effect of a substantial reduction in adrenaline (Epi) particle size to a few micrometres (Epi microcrystals (Epi-MC)) on enhancing adrenaline dissolution and increasing the rate and extent of sublingual absorption from a previously developed rapidly disintegrating sublingual tablet (RDST) formulation in a validated preclinical model. The in-vivo absorption of Epi-MC 20 mg RDSTs and Epi 40 mg RDSTs was evaluated in rabbits. Epi 0.3 mg intramuscular (IM) injection in the thigh and placebo RDSTs were used as positive and negative controls, respectively. Epimean (standard deviation) area under the plasma concentration vs time curves up to 60 min and Cmax from Epi-MC 20 mg and Epi 40 mg RDSTs did not differ significantly (P > 0.05) from Epi 0.3 mg IM injection. After adrenaline, regardless of route of administration, pharmacokinetic parameters were significantly higher (P adrenaline levels). Epi-MC RDSTs facilitated a twofold increase in Epi absorption and a 50% reduction in the sublingual dose. This novel sublingual tablet formulation is potentially useful for the first-aid treatment of anaphylaxis in community settings. © 2014 Royal Pharmaceutical Society.

  6. 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.

  7. Development and evaluation of fixed dose bi therapy sublingual tablets for treatment stress hypertension and anxiety

    Directory of Open Access Journals (Sweden)

    Mohamed A El-Nabarawi

    2013-01-01

    Full Text Available Objective: A stress induced rise in the blood pressure. Some believe that patients with hypertension are characterized by a generalized state of increased anxiety. Aim: The purpose of this study is to prepare a fixed dose bi therapy using bisoprolol hemifumarate (BH as antihypertensive drug and buspirone hydrochloride (BuHCl as anxiolytic drug, which can be used to treat both diseases concomitantly. Using sublingual tablets is hopeful to improve the BuHCl poor oral bioavailability and to facilitate administration to patients experiencing problems with swallowing. Materials and Methods: A total of 5mg BH and 10mg BuHCl were selected based on compatibility study. A 3×22 full factorial design was adopted for the optimization of the tablets prepared by direct compression method. The effects of the filler type, the binder molecular weight, and the binder type were studied. The prepared formulae were evaluated according to their physical characters as hardness, friability, disintegration time (new modified method and in vivo disintegration time and wetting properties. In vitro drugs dissolute, permeation through the buccal mucosa and the effect of storage were analyzed by a new valid high pressure liquid chromatography (HPLC method. Bioavailability study of the selected formula study was carried out and followed by the clinical. Results: The optimized tablet formulation showed accepted average weight, hardness, wetting time, friability, content uniformity, disintegration time (less than 3 min. Maximum drug release could be achieved with in 10 min. In addition enhancing drug permeation through the buccal mucosa and, the maximum concentration of the drug that reached the blood was in the first 10 min which means a rapid onset of action and improved the extent of both drug′s absorption. Conclusion: The results revealed that sublingual (F6 tablets containing both drugs would maintain rapid onset of action, and increase bioavailability. BuHCl with BH

  8. Efficacy of alprazolam sublingual tablets in the treatment of the acute phase of panic disorders.

    Science.gov (United States)

    Márquez, Miguel; Arenoso, Hector; Caruso, Norberto

    2011-01-01

    Panic disorder affects 2-5% of the general population. In Argentina, one million people would be affected with a 91% rate of psychiatric comorbidity. AIM; To compare efficacy parameters between sublingual (ALP-SL) and conventional (ALP-CT) tablets of alprazolam in the treatment of acute phase of panic disorder with and without agoraphobia. A comparative, multicenter (6 sites), double blind, randomized study was carried out. A total of 190 outpatients with (n=117) and without (n=73) agoraphobia were treated with ALP-SL or ALP-CT for 12 weeks. Outcome was assessed with the Clinical Global Impressions (CGI-S/CGI-I), Hamilton Rating Scale for Anxiety (HAM-A), Arizona Sexual Experiences Scale (ASEX), Patient Global Impression (PGI), Psychological General Well-Being Index (PGWBI), Panic Disorder Severity Scale (PDSS) also by the number of panic attacks and extension and intensity of panic attacks and anticipatory anxiety. RESULTS. Both treatments resulted in statistically significant clinical improvement in all measures. ASEX presented no changes during the study. The average dose of alprazolam for 12 weeks was 1.36 ± 0.70 mg/day (1.39 ± 0.77 ALP-CT and 1.33 ± 0.64 ALP-SL). With ALP-SL, panic attacks were shorter (p Alprazolam has been demonstrated to have efficacy, safety and good tolerability in the treatment of the acute phase of panic disorder, the sublingual tablets showing some comparative advantages.

  9. Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Malling, Hans-Jørgen; Montagut, A; Melac, M

    2009-01-01

    BACKGROUND: The optimal dose of grass pollen tablets for sublingual immunotherapy (SLIT) in allergic rhinoconjunctivitis patients was previously established in a multinational, randomized, double-blind, placebo-controlled study in 628 adults. Patients were randomized to receive once-daily 5-grass...... pollen sublingual tablets of 100 IR (index of reactivity), 300 IR or 500 IR, or placebo starting 4 months before the pollen season. OBJECTIVE: The aim of this complementary analysis was to determine whether 300 IR 5-grass pollen SLIT-tablets is effective in different subtypes of patients who are allergic......: The risk-benefit ratio validates the use of 300 IR tablets in clinical practice in all of these patient subgroups, regardless of severity profile, sensitization status and presence of asthma....

  10. Treatment effect of sublingual immunotherapy tablets and pharmacotherapies for seasonal and perennial allergic rhinitis: Pooled analyses.

    Science.gov (United States)

    Durham, Stephen R; Creticos, Peter S; Nelson, Harold S; Li, Ziliang; Kaur, Amarjot; Meltzer, Eli O; Nolte, Hendrik

    2016-10-01

    Data comparing the treatment effect of allergy immunotherapy and pharmacotherapy are lacking. We sought to indirectly compare the treatment effect of sublingual immunotherapy (SLIT)-tablets with pharmacotherapy for seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). Pooled data from randomized, double-blind, placebo-controlled trials for the clinical development programs of selected allergic rhinitis treatments were evaluated. Total nasal symptom scores (TNSSs) relative to placebo were compared. Subjects scored symptoms daily during entire pollen seasons in 6 timothy grass SLIT-tablet trials (n = 3094) and 2 ragweed SLIT-tablet trials (n = 658) and during the last 8 weeks of treatment in 2 house dust mite (HDM) SLIT-tablet trials (n = 1768). Subjects scored symptoms daily in 7 montelukast (10 mg, n = 6799), 9 desloratadine (5 mg, n = 4455), and 8 mometasone furoate nasal spray (MFNS; 200 μg daily, n = 2140) SAR or PAR trials. SLIT-tablet trials allowed rescue medication use, whereas most pharmacotherapy trials did not. A fixed-effect meta-analysis method estimated differences in on-treatment average TNSSs. In grass and ragweed SLIT-tablet trials, overall improvement in TNSSs relative to placebo was 16.3% and 17.1%, respectively. In HDM SLIT-tablet trials, TNSS overall improvement relative to placebo was 16.1%. In the montelukast, desloratadine, and MFNS trials, TNSS overall improvement relative to placebo was 5.4%, 8.5%, and 22.2%, respectively, for SAR trials, and 3.7%, 4.8%, and 11.2%, respectively, for PAR trials. Although comparisons were limited by study design heterogeneity and use of rescue medications in SLIT-tablet trials, effects on nasal symptoms with timothy grass and ragweed SLIT-tablets were nearly as great as with MFNS and numerically greater than with montelukast and desloratadine for SAR. HDM SLIT-tablet effects were numerically greater than all pharmacotherapies for PAR. SLIT-tablets offer the additional

  11. Post-treatment efficacy of discontinuous treatment with 300IR 5-grass pollen sublingual tablet in adults with grass pollen-induced allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Didier, A; Malling, H-J; Worm, Marcel

    2013-01-01

    Sustained efficacy over three pollen seasons of pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet has been demonstrated in adults with moderate-severe grass pollen-associated allergic rhinoconjunctivitis....

  12. Deposition of a model substance, Tc E-HIDA, in the oral cavity after administration of lozenges, chewing gum and sublingual tablets

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Davis, S.S.; Melia, C.D.

    1990-01-01

    The deposition and clearance of a model substance, Tc E-HIDA, in the oral cavity/upper oesophagus and in the stomach after administration of lozenges, chewing gum and sublingual tablets has been followed by gamma scintigraphy in a group of healthy male volunteers. Following administration...... of sublingual tablets, the residence time of the model substance in the oral cavity was significantly longer than following administration of chewing gum. The residence time following administration of lozenges was found to be the shortest....

  13. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis.

    Science.gov (United States)

    Durham, Stephen R; Yang, William H; Pedersen, Martin R; Johansen, Niels; Rak, Sabina

    2006-04-01

    Specific immunotherapy is the only treatment modality that has the potential to alter the natural course of allergic diseases. Sublingual immunotherapy has been developed to facilitate access to this form of treatment and to minimize serious adverse events. To investigate the efficacy and safety of sublingual grass allergen tablets in seasonal allergic rhinoconjunctivitis. A multinational, multicenter, randomized, placebo-controlled trial conducted during 2002 and 2003. Fifty-five centers in 8 countries included 855 participants age 18 to 65 years who gave a history of grass pollen-induced allergic rhinoconjunctivitis and had a positive skin prick test and elevated serum allergen-specific IgE to Phleum pratense. Participants were randomized to 2500, 25,000, or 75,000 SQ-T grass allergen tablets (GRAZAX; ALK-Abelló, Hørsholm, Denmark) or placebo for sublingual administration once daily. Mean duration of treatment was 18 weeks. Average rhinoconjunctivitis scores during the season showed moderate reductions of symptoms (16%) and medication use (28%) for the grass allergen tablet 75,000 SQ-T (P = .0710; P = .0470) compared with placebo. Significantly better rhinoconjunctivitis quality of life scores (P = .006) and an increased number of well days (P = .041) were also observed. Efficacy was increased in the subgroup of patients who completed the recommended preseasonal treatment of at least 8 weeks before the grass pollen season (symptoms, 21%, P = .0020; and medication use, 29%, P = .0120). No safety concerns were observed. This study confirms dose-dependent efficacy of the grass allergen tablet. Although further studies are required, the greater tolerability of the tablet may permit immunotherapy to be available to a much broader group of patients with impaired quality of life caused by grass pollen allergy. For patients with grass pollen allergy, sublingual immunotherapy is well tolerated and can reduce symptoms and improve quality of life.

  14. Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy

    DEFF Research Database (Denmark)

    Valovirta, Erkka; Petersen, Thomas H; Piotrowska, Teresa

    2017-01-01

    BACKGROUND: Allergy immunotherapy targets the immunological cause of allergic rhinoconjunctivitis and allergic asthma and has the potential to alter the natural course of allergic disease. OBJECTIVE: The primary objective was to investigate the effect of the SQ grass sublingual immunotherapy tablet...... compared with placebo on the risk of developing asthma. METHODS: A total of 812 children (5-12 years), with a clinically relevant history of grass pollen allergic rhinoconjunctivitis and no medical history or signs of asthma, were included in the randomized, double-blind, placebo-controlled trial......, comprising 3 years of treatment and 2 years of follow-up. RESULTS: There was no difference in time to onset of asthma, defined by prespecified asthma criteria relying on documented reversible impairment of lung function (primary endpoint). Treatment with the SQ grass sublingual immunotherapy tablet...

  15. [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

  16. Soy polysaccharide as a novel superdisintegrant in sildenafil citrate sublingual tablets: preparation, characterization, and in vivo evaluation

    Directory of Open Access Journals (Sweden)

    Hosny KM

    2015-01-01

    Full Text Available Khaled Mohamed Hosny,1,2 Hisham Ahmed Mosli,3 Ali Habiballah Hassan4 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt; 3Department of Urology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Orthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Sildenafil citrate (SC, a drug used to treat erectile dysfunction, is available in tablet form but has three major problems. First, the drug displays inadequate aqueous solubility, which delays the onset of its action. Second, the drug undergoes extensive first-pass metabolism, resulting in a low (40% bioavailability. Third, the gastrointestinal effects of SC include dyspepsia and a burning sensation. The aim of this research was to prepare SC as a sublingual tablet utilizing soy polysaccharide as novel superdisintegrant to mitigate the abovementioned problems. The solubility of SC in various hydrophilic carrier solutions was estimated in order to prepare the drug as a coprecipitate. Sublingual tablets were prepared and evaluated for hardness, friability, drug content, wetting time, water absorption ratio, in vitro dispersion time, dissolution rate, and stability study. The pharmacokinetic study of the tablets was carried out on healthy volunteers. The results indicated that the co-precipitation of SC with polyvinylpyrollidone K30 enhanced the solubility of SC by more than eight folds. The tablet contained 8% soy polysaccharide as a superdisintegrant and provided a wetting time of 25 seconds, and in vitro dispersion times of 55 seconds. The drug release was found to be 95.6%. The prepared SC sublingual tablet also exhibited a rapid onset of action, and its bioavailability was enhanced 1.68-fold compared with that of the marketed tablets. It

  17. Safety of sublingual immunotherapy Timothy grass tablet in subjects with allergic rhinitis with or without conjunctivitis and history of asthma

    DEFF Research Database (Denmark)

    Maloney, J; Durham, S; Skoner, D

    2015-01-01

    BACKGROUND: Patients with asthma may be more susceptible to adverse events (AEs) with sublingual immunotherapy tablet (SLIT-tablet) treatment, such as severe systemic reactions and asthma-related events. Using data from eight trials of grass SLIT-tablet in subjects with allergic rhinitis with...... with uncontrolled and severe asthma were excluded from the trials. Frequencies for treatment-emergent AEs (TEAEs), local allergic swelling (mouth or throat), systemic allergic reactions, and asthma-related treatment-related AEs (TRAEs) were calculated. RESULTS: Among adults (n = 3314) and children (n = 881), 24......% and 31%, respectively, had reported asthma. No serious local allergic swellings or serious systemic allergic reactions occurred in subjects with asthma treated with SLIT-tablet. There was no evidence of increased TEAEs, systemic allergic reactions, or severe local allergic swellings in adults or children...

  18. Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy.

    Science.gov (United States)

    Valovirta, Erkka; Petersen, Thomas H; Piotrowska, Teresa; Laursen, Mette K; Andersen, Jens S; Sørensen, Helle F; Klink, Rabih

    2017-07-06

    Allergy immunotherapy targets the immunological cause of allergic rhinoconjunctivitis and allergic asthma and has the potential to alter the natural course of allergic disease. The primary objective was to investigate the effect of the SQ grass sublingual immunotherapy tablet compared with placebo on the risk of developing asthma. A total of 812 children (5-12 years), with a clinically relevant history of grass pollen allergic rhinoconjunctivitis and no medical history or signs of asthma, were included in the randomized, double-blind, placebo-controlled trial, comprising 3 years of treatment and 2 years of follow-up. There was no difference in time to onset of asthma, defined by prespecified asthma criteria relying on documented reversible impairment of lung function (primary endpoint). Treatment with the SQ grass sublingual immunotherapy tablet significantly reduced the risk of experiencing asthma symptoms or using asthma medication at the end of trial (odds ratio = 0.66, P year posttreatment follow-up, and during the entire 5-year trial period. Also, grass allergic rhinoconjunctivitis symptoms were 22% to 30% reduced (P years). At the end of the trial, the use of allergic rhinoconjunctivitis pharmacotherapy was significantly less (27% relative difference to placebo, P < .001). Total IgE, grass pollen-specific IgE, and skin prick test reactivity to grass pollen were all reduced compared to placebo. Treatment with the SQ grass sublingual immunotherapy tablet reduced the risk of experiencing asthma symptoms and using asthma medication, and had a positive, long-term clinical effect on rhinoconjunctivitis symptoms and medication use but did not show an effect on the time to onset of asthma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. 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.

  20. Safety of ragweed sublingual allergy immunotherapy tablets in adults with allergic rhinoconjunctivitis.

    Science.gov (United States)

    Nayak, Anjuli S; Atiee, George J; Dige, Ea; Maloney, Jennifer; Nolte, Hendrik

    2012-01-01

    A sublingually administered allergy immunotherapy tablet (AIT) is under development to treat ragweed (Ambrosia artemisiifolia)-induced allergic rhinoconjunctivitis (ARC). This study investigates the optimal tolerable dose of once daily ragweed pollen AIT.Subjects 18-50 years old with ragweed-induced ARC were enrolled at two U.S. centers in a double-blind, placebo-controlled,dose-escalation study outside ragweed season. Groups (12 subjects each) were to be randomized 3:1 to 28 days of active treatment (groups assigned in sequence to 3, 6, 12, 24, 50, or 100 units of Ambrosia artemislifolia major allergen 1 [Amb a 1 U],without dose buildup at any level) or matching placebo. Recruitment to 50 Amb a 1-U was discontinued because of adverse events (AEs) after four AIT subjects were enrolled; 100 Amb a 1-U was not initiated. Fifty-three subjects were randomized (AIT,n = 40; placebo, n = 13); four discontinued, all because of AEs (AIT, n = 3; placebo, n = 1). Treatment-related AEs (TRAEs) were more frequent with AIT (73%) than placebo (31%), increasing with dose level. AIT TRAEs were mostly mild (94%) or moderate(5%). No serious TRAEs or anaphylactic shock occurred. The most common TRAEs with AIT were localized pruritus, nasal irritation, and throat irritation. Median onset for common AIT application site reactions was 24 ≤ hours after first treatment (median duration, 15-50 minutes). AIT increased immunoglobulin (Ig) significantly more than placebo (ragweed-specific IgE [6, 12, and 24 Amb a 1-U]; IgG4 [all doses]; p < 0.05). Three subjects in dose groups ≥ 24 Amb a 1-U experienced symptoms suggestive of systemic reaction. Of tested doses, ragweed AIT 24

  1. Influence of food on pharmacokinetics of zolpidem from fast dissolving sublingual zolpidem tartrate tablets.

    Science.gov (United States)

    Greenblatt, David J; Harmatz, Jerold S; Singh, Nikhilesh N; Roth, Thomas; Harris, Stephen C; Kapil, Ram P

    2013-11-01

    Ingesting food can impact the pharmacokinetics of sedative-hypnotic drugs. A buffered zolpidem sublingual tablet (ZST) recently became available for the treatment of middle-of-the-night awakening. In this randomized, open-label, single-site study, the pharmacokinetic profile of ZST was evaluated when administered while fasting and following a standard high-fat meal (fed state). Healthy adults aged 18-64 years received a single morning dose of 3.5 mg ZST in the fed or fasting state. From 20 min to 3 h post-dose, zolpidem plasma levels were lower in the fed state compared to the fasting state. After 4 h post-dose (corresponding to "morning wake time"), higher zolpidem plasma levels were evident in the fed state. Area under the concentration-time curve (AUC) values for the 0-8 h interval were 160 ng/mL h in the fed state and 203 ng/mL h in the fasting state (P fasting states, Cmax was 32.0 ng/mL versus 57.3 ng/mL (P < .001), respectively, and Tmax was 3.0 h versus 0.92 h (P < .001), respectively. Together these data suggest that administration of ZST in the fed state is not optimal for maximizing the likelihood of therapeutic benefit and minimizing the probability of residual sedation. © 2013, The American College of Clinical Pharmacology.

  2. Opioid substitution treatment with sublingual buprenorphine in Manipur and Nagaland in Northeast India: what has been established needs to be continued and expanded

    Directory of Open Access Journals (Sweden)

    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.

  3. Efficacy and safety of sublingual fentanyl orally disintegrating tablets in patients with breakthrough pain: multicentre prospective study.

    Science.gov (United States)

    Guitart, Jordi; Vargas, Isabel; De Sanctis, Vicente; Ferreras, Julia; Fuentes, Jose; Salazar, Rafael; Vázquez, Juan M; Folch, Jordi; Moya, Jordi; Ribera, Hermann; Rodelas, Francisco; Tomás, Albert; Arilla, María; Coma, Joan; Aberasturi, Teresa; Sintes, Dolores; Lombán, Ester

    2013-09-01

    The aim of this study was to evaluate the effectiveness and safety of sublingual fentanyl oral disintegrating tablets (sublingual fentanyl ODT) for the treatment of breakthrough pain (BTP), cancer or non-cancer related, in terms of relief of pain intensity, adverse events (AEs) and patient satisfaction, and to further examine the clinical and epidemiological profile of patients with BTP in a clinical setting. A multicentre, prospective, open-label study was conducted in 19 pain units from Catalonia hospitals (Spain) over a 1-month period. Opioid-tolerant adult patients experiencing episodes of BTP intensity >5 on a visual analogue scale (VAS) during the 12-24 h before screening or AEs related to their previous rescue medication for BTP received sublingual fentanyl ODT in the course of routine clinical practice and completed a 30-day study period consisting of five assessment points: days 0 (baseline), 3, 7, 15 and 30. The efficacy was assessed by collecting pain intensity and pain relief data at baseline and at each assessment. AEs were recorded by investigators throughout the study during clinic visits and telephone follow-ups. For all patients, titration was begun with an initial dose of 100 μg. No more than two doses were allowed to treat an episode and patients might wait at least 4 h before treating another BTP episode with sublingual fentanyl ODT. The dose was increased by 100 μg multiples up to 400 μg as needed; and by 200 μg multiples up from 400 to 800 μg, the maximum titration step. A total of 182 patients were enrolled and 177 (97.2 %) completed the study: 37 had breakthrough cancer pain (BTcP) and 145 had breakthrough non-cancer pain (BTncP). The mean pain intensity showed a statistically significant improvement at the first assessment point and at all assessments thereafter (p < 0.0001). At the end of the study, the time lag between administration and first effect of sublingual fentanyl ODT was ≤10 min in 69.0 % (60 % BTcP and 71.2 % BTncP). The

  4. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis

    NARCIS (Netherlands)

    Dahl, Ronald; Kapp, Alexander; Colombo, Giselda; deMonchy, Jan G. R.; Rak, Sabina; Emminger, Waltraud; Rivas, Montserrat Fernandez; Ribel, Mette; Durham, Stephen R.

    Background: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking.

  5. Safety and tolerability of grass pollen tablets in sublingual immunotherapy--a phase-1 study

    DEFF Research Database (Denmark)

    Larsen, T H; Poulsen, Lars K.; Melac, M

    2006-01-01

    A single-centre, randomized, double-blind, placebo-controlled study. Aims: To compare the safety and tolerability of four different sublingual immunotherapy (SLIT) regimes in grass pollen allergic rhinitis....

  6. Major allergen content consistency of SQ house dust mite sublingual immunotherapy tablets and relevance across geographic regions.

    Science.gov (United States)

    Nolte, Hendrik; Plunkett, Greg; Grosch, Karin; Larsen, Jorgen Nedergaard; Lund, Kaare; Bollen, Mirko

    2016-09-01

    Consistency in composition and potency, particularly regarding major allergens, is crucial for the quality of extracts for allergen immunotherapy. To characterize the major allergen composition of house dust mite (HDM) extracts commercially available in the United States and the SQ HDM sublingual immunotherapy (SLIT) tablet, and to relate the composition to patient sensitization patterns. Der 1/Der 2 ratios were determined in 10,000- and 30,000-AU/mL HDM extracts from 5 US companies and the SQ HDM SLIT-tablet. Allergen content was analyzed by enzyme-linked immunosorbent assay and compared with an in-house reference. Sensitivity toward Der p 1, Der p 2, and Der p 10 was determined in serum from randomly selected subgroups of 220 individuals from North American and European SQ HDM SLIT-tablet trials. Mean Der 1/Der 2 ratios in US HDM extracts ranged from 0.4 to 20.5. For the SQ HDM SLIT-tablet (20 batches), variability did not exceed 12% regarding content of Der f 1 (SD, 11.9%; 95% confidence interval [CI], 0.94-1.06), Der p 1 (SD, 6.1%; 95% CI, 0.97-1.03), and combined Der 2 allergen (SD, 6.4%; 95% CI, 0.97-1.03), indicating a consistent Der 1/Der 2 ratio. High allergen sensitivity frequencies toward Der p 1 and Der p 2 were observed regardless of geographic region. Efficacy of the SQ HDM SLIT-tablet has been demonstrated in 5 clinical trials. The SQ HDM SLIT-tablet has efficacy potential for a broad range of patients because it includes a consistent 1:1 ratio of the 2 major HDM allergens to which individuals were most frequently sensitized across geographic regions. Efficacy has been demonstrated. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. 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

  8. SQ grass sublingual allergy immunotherapy tablet for disease-modifying treatment of grass pollen allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Dahl, Ronald; Roberts, Graham; de Blic, Jacques

    2016-01-01

    America and throughout Europe for the treatment of adults and children (≥5 years old) with grass pollen-induced ARC. OBJECTIVE: The clinical evidence for the use of SQ grass SLIT-tablet as a disease-modifying treatment for grass pollen ARC is discussed in this review. METHODS: The review included...... the suitability of SQ grass SLIT-tablet for patients with clinically relevant symptoms to multiple Pooideae grass species, single-season efficacy, safety, adherence, coseasonal initiation, and cost-effectiveness. The data from the long-term SQ grass SLIT-tablet clinical trial that evaluated a clinical effect 2...

  9. Breakthrough Pain Management with Sublingual Fentanyl Tablets in Patients with Cancer: Age Subgroup Analysis of a Multicenter Prospective Study.

    Science.gov (United States)

    Guitart, Jordi; Vargas, María Isabel; De Sanctis, Vicente; Folch, Jordi; Salazar, Rafael; Fuentes, José; Coma, Joan; Ferreras, Julia; Moya, Jordi; Tomás, Albert; Estivill, Pere; Rodelas, Francisco; Jiménez, Antonio Javier; Sanz, Almudena

    2017-09-01

    Breakthrough pain (BTP) management in patients with cancer is challenging, especially in the elderly. However, no studies examining the influence of age on BTP medication have been conducted. The aim of this work was to investigate the effect of sublingual fentanyl tablets (SFTs) in terms of efficacy, safety, and quality of life in two age categories. We performed age subgroup analyses (Pain intensity (PI), onset of pain relief, frequency and duration of BTP episodes, and adverse events (AEs) were assessed at 3, 7, 15, and 30 days. Health-status instruments used were the Short Form 12, version 2 (SF-12v2) questionnaire, and the Hospital Anxiety and Depression Scale (HADS-A and HADS-D). Twenty-six patients were aged 65 years. Most patients experienced one to five daily episodes after 30 days, and <5% needed a treatment change. AEs were less frequently reported in older individuals (20.5 vs. 36.4%). Age subgroup analyses suggest that SFTs are an effective and safe treatment for the management of BTP in cancer patients of all ages. SFTs may offer a well-tolerated and efficient option to control cancer BTP in the elderly.

  10. Determination of degradation products and process related impurities of asenapine maleate in asenapine sublingual tablets by UPLC

    Science.gov (United States)

    Kumar, Nitin; Sangeetha, D.; Kalyanraman, L.

    2017-11-01

    For determination of process related impurities and degradation products of asenapine maleate in asenapine sublingual Tablets, a reversed phase, stability indicating UPLC method was developed. Acetonitrile, methanol and potassium dihydrogen phosphate buffer with tetra-n- butyl ammonium hydrogen sulphate as ion pair (pH 2.2; 0.01 M) at flow rate of 0.2 ml/min were used in gradient elution mode. Separation was achieved by using acquity BEH Shield RP18 column (1.7 μm, 2.1 mm×100 mm) at 35 ºC. UV detection was performed at 228 nm. Subsequently the liquid chromatography method was validated as per ICH. The drug product was exposed to the stress conditions of acid hydrolysis, base hydrolysis, water hydrolysis, oxidative, thermal, and photolytic. In oxidative stress and thermal stress significant degradation was observed. All the degradation products were well separated from analyte peak and its impurities. Stability indicating nature of the method was proved by demonstrating the peak purity of Asenapine peak in all the stressed samples. The mass balance was found >95% for all the stress conditions. Based on method validation, the method was found specific, linear, accurate, precise, rugged and robust.

  11. Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Wahn, Ulrich; Tabar, Ana; Kuna, Piotr

    2009-01-01

    of this tablet in children and adolescents with grass pollen-related allergic rhinitis. METHODS: In this multinational, randomized, double-blind, placebo-controlled study, 278 children (5-17 years of age) with grass pollen-related rhinoconjunctivitis (confirmed by means of a positive grass pollen skin prick test...

  12. Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years

    NARCIS (Netherlands)

    Dahl, Ronald; Kapp, Alexander; Colombo, Giselda; De Monchy, Jan G. R.; Rak, Sabina; Emminger, Waltraud; Riis, Bente; Gronager, Pernille M.; Durham, Stephen R.

    Background: This is an interim analysis of a randomized, double-blind, placebo-controlled phase III trial with 3 years of daily treatment with grass tablet immunotherapy (GRAZAX; ALK-Abello A/S, Horsholm, Denmark) or placebo, followed by 2 years of follow-up to assess the persistent efficacy.

  13. Efficacy and safety of sublingual fentanyl orally disintegrating tablet at doses determined from oral morphine rescue doses in the treatment of breakthrough cancer pain.

    Science.gov (United States)

    Shimoyama, Naohito; Gomyo, Ikuo; Teramoto, Osamu; Kojima, Keisuke; Higuchi, Hitomi; Yukitoshi, Nobuyuki; Ohta, Eri; Shimoyama, Megumi

    2015-02-01

    A randomized, crossover, double-blinded placebo-controlled and non-blinded active drug-controlled, comparative clinical trial was conducted to evaluate the efficacy and safety of sublingual fentanyl tablet. Subjects were patients treated with strong opioids at fixed intervals for chronic cancer pain and with oral morphine as rescue medication for breakthrough pain. Sublingual fentanyl was administered at doses that were 1/25th (high dose) and 1/50th (low dose) of the dose of rescue morphine and was compared with placebo and oral morphine. The primary endpoint was pain intensity difference at 30 min after administration. (Clinical Trials Government; NCT00684632). Fifty-one patients were enrolled in the investigation. Their mean pain intensity in visual analog scale before rescue medication prior to the investigation was 60.96 (16.44, standard deviation) mm. Compared with placebo, the low and high doses of sublingual fentanyl showed significant analgesic effects (least squares mean difference, 4.54 and 8.49 mm; P = 0.014, P pain and with oral morphine at doses up to 20 mg as rescue medication were investigated. The doses of sublingual fentanyl to treat breakthrough pain were determined from rescue morphine doses by use of conversion ratios. In these patients, administration of sublingual fentanyl at doses determined by a conversion ratio of 1/50 was effective and safe. Further studies are needed to validate the use of this conversion method. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. 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

  15. Sublingual Fentanyl Tablets for Relief of Breakthrough Pain in Cancer Patients and Association with Quality-of-Life Outcomes.

    Science.gov (United States)

    Guitart, Jordi; Vargas, María Isabel; De Sanctis, Vicente; Folch, Jordi; Salazar, Rafael; Fuentes, José; Coma, Jordi; Ferreras, Julia; Moya, Jordi; Tomás, Albert; Estivill, Pere; Rodelas, Francisco; Jiménez, Antonio Javier

    2015-12-01

    Breakthrough pain (BTP) is highly prevalent in patients with cancer and is strongly associated with adverse outcomes related to health status, mood, anxiety and depression. However, studies on the effect of BTP medication on quality of life (QOL) are lacking. The purpose of this study was to provide a qualitative evaluation of the effect of sublingual fentanyl tablets (SFT), a therapy specifically developed for BTP, on the QOL of cancer pain patients. We conducted a multicentre, prospective observation post-authorisation, open-label study between March and December 2013. The study consisted of a screening visit and four assessment points at 3, 7, 15 and 30 days. Pain intensity (PI), frequency of BTP, onset of pain relief and adverse events (AEs) were assessed at each visit. Anxiety and depression were evaluated using the validated Hospital Anxiety and Depression Scale (HADS) and health status using the Short Form 12, version 2 (SF-12v2) Health Survey. Of the 102 patients considered eligible, 81 (79.4 %) were enrolled; of these, 69 (85.1 %) completed the study. Significant pain reduction was achieved for average PI (p < 0.001) compared with baseline. At the end of the observational period, HADS scores showed significant improvement in the depression subscale (p = 0.005) and the anxiety subscale (p < 0.001). Similarly, SF-12 scores showed significant improvement, both in the mental component score (p < 0.001) and the physical component score (p = 0.002). SFT was well-tolerated and only one patient withdrew from the study due to drug-related AEs. SFT represents an effective, well-tolerated treatment for cancer BTP. Results provide consistent evidence for the positive impact of SFT on health-related QOL and physical functioning as well as other co-morbidities of cancer BTP such as anxiety and depression.

  16. 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.

  17. SQ house dust mite sublingually administered immunotherapy tablet (ALK) improves allergic rhinitis in patients with house dust mite allergic asthma and rhinitis symptoms

    DEFF Research Database (Denmark)

    Mosbech, Holger; Canonica, G Walter; Backer, Vibeke

    2015-01-01

    BACKGROUND: House dust mite (HDM) allergy is associated with persistent allergic rhinitis (AR) and allergic asthma. OBJECTIVE: To investigate the efficacy and safety of a SQ HDM sublingually administered immunotherapy tablet (ALK, Hørsholm, Denmark) in adults and adolescents with HDM respiratory...... allergic disease and report the AR results. METHODS: Six hundred four subjects at least 14 years old with HDM AR and mild to moderate HDM allergic asthma were randomized 1:1:1:1 to double-blinded daily treatment with 1, 3, 6 SQ-HDM or placebo. End-of-treatment rhinoconjunctivitis symptoms and medication...... score were predefined extrapulmonary end points. A subgroup analysis was conducted post hoc in subjects with a total combined rhinitis score (TCRS) > 0 (ie, with AR symptoms and/or AR medication use during the 4-week baseline period). The subgroup was comprised of 498 subjects (82%). RESULTS...

  18. Fentanyl Sublingual Tablets Versus Subcutaneous Morphine for the Management of Severe Cancer Pain Episodes in Patients Receiving Opioid Treatment: A Double-Blind, Randomized, Noninferiority Trial.

    Science.gov (United States)

    Zecca, Ernesto; Brunelli, Cinzia; Centurioni, Fabio; Manzoni, Andrea; Pigni, Alessandra; Caraceni, Augusto

    2017-03-01

    Purpose Fentanyl sublingual tablets (FST) are a potentially useful alternative to parenteral opioids such as subcutaneous morphine (SCM) to treat severe cancer pain episodes. No direct comparison between FST and SCM is available. The aim of this study was to test noninferiority of FST versus SCM during the first 30 min postadministration. Methods Patients receiving stable opioid therapy and experiencing a severe pain episode were randomly assigned to either 100 µg FST or 5 mg SCM in a double-blind, double-dummy trial. Average pain intensity (PI) assessed on a 0 to 10 numerical rating scale at 10, 20, and 30 min postadministration was the main end point. Analysis of covariance, adjusted by baseline PI, was the main analysis. The noninferiority margin (NIm) for the between-group difference was set at -0.6, that is, equal to one third of the minimum clinically important PI difference of two points. Results A total of 114 patients were randomly assigned to either FST (n = 58) or SCM (n = 56). One patient (in the FST group) withdrew consent before drug administration and was excluded from analysis. Baseline mean PIs were 7.5 in both groups; mean average PIs assessed at 10, 20, and 30 min postadministration were 5.0 and 4.5 for FST and SCM, respectively, with the 95% CI of the between-group difference including the NIm (-0.49; 95% CI, -1.10 to 0.09). Patients taking FST received a second drug dose after 30 min more frequently than did patients taking SCM (51% v 37%, respectively; risk difference, -13%; 95% CI, -30% to 3%). Both treatments were well tolerated, with average follow-up adverse event scores below the response of "A Little." Ninety-three percent of patients preferred the sublingual administration. Conclusion This trial did not show noninferiority of FST versus SCM within the chosen NIm. Both treatments were safe, and patients preferred the sublingual route of administration. FST provides analgesia with modest to moderate increased risk of lower efficacy

  19. Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen-induced rhinoconjunctivitis.

    Science.gov (United States)

    Didier, Alain; Worm, Margitta; Horak, Friedrich; Sussman, Gordon; de Beaumont, Olivier; Le Gall, Martine; Melac, Michel; Malling, Hans-Jorgen

    2011-09-01

    Seasonal allergic rhinoconjunctivitis affects millions of persons. The efficacy of allergen sublingual immunotherapy (SLIT) was demonstrated in previous short-term studies. We sought to evaluate the sustained efficacy of 2 dosing regimens of a pre- and coseasonal treatment with 300 IR (index of reactivity) 5-grass-pollen SLIT tablets (Oralair) compared with placebo assessed by using the average adjusted symptom score (AAdSS) at season 3 in adults with grass pollen-induced rhinoconjunctivitis. Six hundred thirty-three patients were treated for either 2 or 4 months before and then during the grass pollen season with active or placebo treatment for 3 consecutive seasons. The primary outcome was the AAdSS, a symptom score adjusted for rescue medication use, after 3 consecutive treatment seasons. Secondary outcomes were symptoms and rescue medication score, quality-of-life, and safety assessments. The mean AAdSS was reduced by 36.0% and 34.5% at season 3 in the 2- and 4-month pre- and coseasonal active treatment groups, respectively, compared with that in the placebo group (P ISSs and the medication score, with a marked improvement in quality of life for both active groups compared with the placebo group at season 3. Most treatment-emergent adverse events were local reactions expected with SLIT, decreasing in number and intensity in each treatment season. Sustained efficacy of 2- and 4-month pre- and coseasonal treatment with the 300 IR tablet over 3 pollen seasons was demonstrated, with reduction in symptoms and rescue medication use. The treatment was well tolerated. Adverse events decreased in number and intensity over the 3 seasons. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  20. Satisfaction and quality of life of allergic patients following sublingual five-grass pollen tablet immunotherapy in Spain

    Directory of Open Access Journals (Sweden)

    Darío Antolín-Amerigo

    2017-11-01

    Full Text Available Abstract Background: Five-grass pollen tablet is an effective and well-tolerated therapy for patients with allergic rhinoconjunctivitis (ARC. This trial sought to determine the satisfaction and health-related quality of life (HRQoL of patients undergoing this treatment. Methods: This was a cross-sectional, multicentre, observational, naturalistic study, following a discontinuous pre- and coseasonal five-grass pollen regimen over two seasons in Spain (2012, 2013. The HRQoL of the patients was measured with the specific Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ for adults, adolescent (AdolRQLQ, or paediatric (PRQLQ patients. Treatment satisfaction was assessed by the Satisfaction Scale for Patients Receiving Allergen Immunotherapy (ESPIA questionnaire. Patients/investigators were surveyed on beliefs and attitudes towards the five-grass pollen tablet. ARC evolution according to allergic rhinitis and its impact on asthma (ARIA criteria and treatment adherence were evaluated. Results: Among the 591 ARC patients included, the mean (SD HRQoL scores were 1.40 (1.1 in adults, 1.33 (1.1 in adolescents, and 1.15 (1.1 in children, indicating low levels of impairment (scale 0–6. ESPIA answers showed high levels of satisfaction, with an average score of 69.2 (scale 0–100. According to ARIA criteria, 88.2% of patients reported improvement of ARC. Moreover, this was accompanied by a reduced use of symptomatic medication. Adherence to treatment was estimated at 96.8%. In general, both patients and specialists exhibited a positive attitude towards five-grass pollen tablet treatment. Conclusion: ARC patients treated with five-grass pollen tablet showed favourable levels of HRQoL and treatment satisfaction, with concomitant improvements in ARC and symptomatic medication use, which translated into high levels of treatment adherence and a positive attitude towards five-grass pollen tablet.

  1. Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen-induced rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Didier, Alain; Worm, Margitta; Horak, Friedrich

    2011-01-01

    Seasonal allergic rhinoconjunctivitis affects millions of persons. The efficacy of allergen sublingual immunotherapy (SLIT) was demonstrated in previous short-term studies.......Seasonal allergic rhinoconjunctivitis affects millions of persons. The efficacy of allergen sublingual immunotherapy (SLIT) was demonstrated in previous short-term studies....

  2. 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

  3. 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

  4. 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

  5. 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 ...

  6. 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

  7. 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.

  8. Sublingual vs. Oral Captopril in Hypertensive Crisis.

    Science.gov (United States)

    Kaya, Adnan; Tatlisu, Mustafa Adem; Kaplan Kaya, Tugba; Yildirimturk, Ozlem; Gungor, Baris; Karatas, Baran; Yazici, Selcuk; Keskin, Muhammed; Avsar, Sahin; Murat, Ahmet

    2016-01-01

    There are confusing data in literature regarding oral and sublingual captopril effects over blood pressure (BP) decrease. In our study we compared oral and sublingual captopril effectiveness over BP decrease in patients admitted to our Emergency Department with hypertensive urgency. Our study was conducted from January 2012 to January 2013 in patients with hypertensive urgency. In this cross-sectional study after two initial BP measurements, patients were identified as eligible for the study. An initial electrocardiogram was obtained and blood samples were drawn. A total of 212 patients were accepted as eligible for the study, and 25 mg of captopril was randomly given orally or sublingually; BP was measured at 10, 30, and 60 min. We selected the patients to the groups consecutively. A 25% reduction of initial BP 1 h after initiation of the treatment was accepted as an accomplishment. A second 25 mg of captopril was given if the target of 25% reduction of BP was not reached after the first tablet. Intravenous drugs were administered to the patients resistant to the captopril and these patients were excluded from the study. The 10-min systolic BP (SBP), diastolic BP, and mean BP (MBP) decrease was more prominent in the sublingual captopril group (p  0.05). In our study, sublingual captopril was found to decrease BP more efficiently in the first 30 min, but this difference equalized at 60 min. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Fentanyl Sublingual Spray

    Science.gov (United States)

    Fentanyl sublingual spray is used to treat breakthrough pain (sudden episodes of pain that occur despite round ... effects of the medication) to narcotic pain medications. Fentanyl is in a class of medications called narcotic ( ...

  10. 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 .).

  11. 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 ...

  12. 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 ...

  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. Sublingual allergen immunotherapy

    DEFF Research Database (Denmark)

    Calderón, M A; Simons, F E R; Malling, Hans-Jørgen

    2012-01-01

    -presenting cells (mostly Langerhans and myeloid dendritic cells) exhibit a tolerogenic phenotype, despite constant exposure to danger signals from food and microbes. This reduces the induction of pro-inflammatory immune responses leading to systemic allergic reactions. Oral tissues contain relatively few mast......To cite this article: Calderón MA, Simons FER, Malling H-J, Lockey RF, Moingeon P, Demoly P. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergy 2012; 67: 302-311. ABSTRACT: Allergen immunotherapy reorients inappropriate immune responses...... in allergic patients. Sublingual allergen immunotherapy (SLIT) has been approved, notably in the European Union, as an effective alternative to subcutaneous allergen immunotherapy (SCIT) for allergic rhinitis patients. Compared with SCIT, SLIT has a better safety profile. This is possibly because oral antigen...

  15. 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.

  16. 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.

  17. [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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate

    Directory of Open Access Journals (Sweden)

    Allam A

    2016-08-01

    Full Text Available Ayat Allam, Gihan Fetih Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt Abstract: The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug’s bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to surfactant ratios. The niosomes were characterized for size, zeta-potential, and entrapment efficiency. The selected niosomal formulation was incorporated into polymeric films using hydroxypropyl methyl cellulose E15 and methyl cellulose as film-forming polymers and Avicel as superdisintegrant. The physical characteristics (appearance, texture, pH, uniformity of weight and thickness, disintegration time, and palatability of the prepared films were studied, in addition to evaluating the in vitro drug release, stability, and in vivo pharmacokinetics in rabbits. The release of the drug from the medicated film was fast (99.9% of the drug was released within 30 minutes, while the drug loaded into the niosomes, either incorporated into the film or not, showed only 22.85% drug release within the same time. The selected sublingual film showed significantly higher rate of drug absorption and higher drug plasma levels compared with that of commercial oral tablet. The plasma levels remained detectable for 24 hours following sublingual administration, compared with only 12 hours after administration of the oral tablet. In addition, the absolute bioavailability of the drug (ie, relative to intravenous administration following sublingual administration was found to be significantly higher (91.06%±13.28%, as compared with that after oral tablet administration (39.37%±11.4%. These results indicate that the fast dissolving niosomal film could be a promising delivery system to

  5. 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

  6. Tumors of the sublingual gland

    DEFF Research Database (Denmark)

    Andreasen, Simon; Bjørndal, K; Agander, T K

    2016-01-01

    Tumors of the salivary glands are a heterogeneous group of diseases most often originating in the major salivary glands. Only a minor proportion of mainly malignant tumors arise in the sublingual gland. Due to the rarity of sublingual gland tumors (SGTs), little is known about the clinicopathologic...... characteristics, prognostic factors, and clinical course. We present a large national series of histopathologically revised SGTs from the past 35 years in Denmark with clinicopathologic correlation. Twenty nine cases were identified, of which 96.6 % were malignant and 16/28 (57.1 %) were adenoid cystic carcinomas...... (ACC). Patient demography was similar to salivary gland tumors in other locations. All fine needle aspiration cytologies (FNACs) interpreted as benign were from ACCs. Metastatic disease was found in 12.5 % of ACCs at diagnosis with one third of all ACC patients having metastases at the end of follow...

  7. 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.

  8. Clinical Applications of Sublingual Immunotherapy.

    Science.gov (United States)

    Edwards, Thomas S; Wise, Sarah K

    2017-12-01

    Sublingual immunotherapy (SLIT) is effective for the treatment of allergic rhinitis and allergic asthma in adults and children. In a limited number of studies, SLIT efficacy has been demonstrated for the treatment of food allergy. SLIT has a higher safety profile versus subcutaneous immunotherapy, although some systemic reactions have been reported. Appropriate patient selection, meticulous patient education, and routine follow-up are key for the safe and effective administration of SLIT. With organization and attention to detail, adding SLIT to one's practice can provide a highly valued patient service. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Sublingual immunotherapy for allergic rhinitis: where are we now?

    Science.gov (United States)

    Incorvaia, Cristoforo; Mauro, Marina; Ridolo, Erminia

    2015-01-01

    Sublingual immunotherapy (SLIT) was introduced in the 1980s as a safer option to subcutaneous immunotherapy and in the latest decade achieved significant advances. Its efficacy in allergic rhinitis is supported by a number of meta-analyses. The development of SLIT preparations in tablets to fulfill the requirements of regulatory agencies for quality of allergen extracts made available optimal products for grass-pollen-induced allergic rhinitis. Preparations of other allergens based on the same production methods are currently in progress. A notable outcome of SLIT, that is shared with subcutaneous immunotherapy, is the evident cost-effectiveness, showing significant cost savings as early as 3 months from starting the treatment, that become as high as 80% compared with drug treatment in the ensuing years.

  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. 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.

  12. 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

  13. Crushed sublingual versus oral ticagrelor administration strategies in patients with unstable angina. A pharmacokinetic/pharmacodynamic study.

    Science.gov (United States)

    Niezgoda, Piotr; Sikora, Joanna; Barańska, Malwina; Sikora, Adam; Buszko, Katarzyna; Siemińska, Emilia; Marszałł, Michał Piotr; Siller-Matula, Jolanta M; Jilma, Bernd; Alexopoulos, Dimitrios; Fabiszak, Tomasz; Kubica, Jacek

    2017-04-03

    Oral administration of crushed ticagrelor tablets turned out to be an efficacious method that improves its pharmacokinetics and pharmacodynamics. This strategy, however, is unlikely to eliminate the drug-drug interaction in patients receiving intravenous morphine, as the impairment of the P2Y12 inhibitor absorption related to decreased propulsive motility of the gastro-intestinal tract is the most likely mechanism of interaction. Thus, we designed a pharmacokinetic and pharmacodynamic study setting the feasibility of platelet inhibition with a loading dose of ticagrelor given as crushed tablets sublingually compared with two other ticagrelor loading dose administration strategies: integral tablet given orally and crushed tablet given orally in patients with unstable angina. Ticagrelor and its metabolite AR-C124900XX plasma concentration was evaluated in nine time points (time frame of 6 hours) using liquid chromatography coupled with mass spectrometry; platelet reactivity was evaluated using multiple electrode aggregometry. The area under the plasma concentration-time curve for ticagrelor and AR-C124900XX was significantly higher in patients treated with crushed tablets given orally compared with crushed tablets given sublingually only within the first hour after loading dose (936.9 ± 898.0 vs 368.0 ± 422.4, p=0.042 and 103.4 ± 120.8 vs 31.3 ± 43.9, p=0.031, respectively). Moreover, we showed significantly stronger platelet inhibition in patients receiving crushed ticagrelor orally vs. sublingually at 30 and 45 min after the loading dose (p=0.024 and p=0.016, respectively). Therefore, the administration strategy of ticagrelor determines the pharmacokinetic and pharmacodynamic profile of both ticagrelor and its active metabolite AR-C124900XX.

  14. Once-daily sublingual allergen-specific immunotherapy improves quality of life in patients with grass pollen-induced allergic rhinoconjunctivitis: a double-blind, randomised study.

    Science.gov (United States)

    Rak, Sabina; Yang, William H; Pedersen, Martin R; Durham, Stephen R

    2007-03-01

    The effect of sublingual immunotherapy on quality of life (QoL) was examined in patients with grass pollen-induced rhinoconjunctivitis. Patients (n = 855) were randomised to once-daily grass allergen tablets (2,500; 25,000; or 75,000 SQ-T Phleum pratense extract; GRAZAX or placebo. Treatment was initiated 8 weeks before the start of the grass pollen season and continued throughout. If symptoms were present, patients received loratadine or placebo rescue medication. There were three major findings: in patients using loratadine, grass allergen tablets provided QOL benefits over placebo; Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score was 17% (p = 0.006) and 20% (p = 0.020) greater with 75,000 SQ-T tablet than with placebo at first and second seasonal visit, respectively; in patients not using loratadine, grass allergen tablets improved QoL more than placebo; RQLQ score was 21% greater (p = 0.021) with 75,000 SQ-T tablet at second seasonal visit; grass tablets (without loratadine) had a greater effect on QoL than loratadine alone. RQLQ score was 26% (p = 0.014) greater with 75,000 SQ-T tablets than loratadine at second seasonal visit. These data show that sublingual immunotherapy with grass allergen tablets improves QOL in allergic rhinoconjunctivitis, reduces symptoms, and that this effect is greater than rescue antihistamine alone.

  15. 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

  16. Sublingual immunotherapy: World Allergy Organization position paper 2013 update

    NARCIS (Netherlands)

    G.W. Canonica (Giorgio Walter); L. Cox (Linda); R. Pawankar (Ruby); C.E. Baena-Cagnani (Carlos); M.S. Blaiss (Michael); S. Bonini (Sergio); J. Bousquet (Jean); M. Calderon (Moises); E. Compalati (Enrico); S.R. Durham (Stephen); R. Gerth van Wijk (Roy); D. Larenas-Linnemann (Désirée); H. Nelson (Harold); G. Passalacqua (Giovanni); O. Pfaar (Oliver); K. Rosario (Karyna); D. Ryan (Dermot); L. Rosenwasser (Lanny); P. Schmid-Grendelmeier (Peter); G.E. Senna (Gianenrico); E. Valovirta (Erkka); H.P. van Bever (Hugo); P. Vichyanond (Pakit); U. Wahn (Ulrich); O.M. Yusuf (Osman)

    2014-01-01

    textabstractWe have prepared this document, "Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update", according to the evidence-based criteria, revising and updating chapters of the originally published paper, "Sublingual Immunotherapy: World Allergy Organization Position

  17. 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

  18. 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.

  19. 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

  20. Tinnitus after administration of sublingual immunotherapy

    DEFF Research Database (Denmark)

    Juel, Jacob

    2017-01-01

    , for example, itching, swelling, irritation, ulceration of the oropharynx and nausea, abdominal pain, diarrhoea, and vomiting. More severe side effects are dominated by systemic and respiratory tract manifestations. RESULTS: In this clinical case, the author reports a right-sided transient tinnitus lasting...... for 48 h after administration of sublingual immunotherapy for house dust mite in allergic rhinitis. CONCLUSIONS: This case provide important insights for clinical practice, as tinnitus has not been previously reported as a side effect of sublingual immunotherapy with house dust mite allergens....

  1. Tinnitus after administration of sublingual immunotherapy

    DEFF Research Database (Denmark)

    Juel, Jacob

    2017-01-01

    BACKGROUND/OBJECTIVES: Sublingual immunotherapy was first described in 1986. Since then, its use has been increased as an alternative to subcutaneously administered immunotherapy in the treatment of allergic rhinitis. The most common side effects are of oropharyngeal and gastrointestinal in natur...

  2. Treatment of respiratory allergy with allergy immunotherapy tablets.

    Science.gov (United States)

    Bachert, C

    2011-07-01

    Allergy immunotherapy tablets (AIT) have expanded the treatment options for patients suffering from respiratory allergies. Efficacy is established in adults and children for two different commercially available grass AITs. The ALK grass AIT has an efficacy comparable to subcutaneous immunotherapy (SCIT), with a proven disease-modifying effect after treatment completion. Safety profiles favour AIT over SCIT. Studies suggest that tablets in all aspects are superior to sublingual drops. AITs for other allergies including house dust mite and birch and ragweed pollen are in development. © 2011 John Wiley & Sons A/S.

  3. 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.

  4. Cost-minimization analysis of sublingual immunotherapy versus subcutaneous immunotherapy for house dust mite respiratory allergic disease in Denmark.

    Science.gov (United States)

    Rønborg, Steen; Johnsen, Claus R; Theilgaard, Sune; Winther, Anders; Hahn-Pedersen, Julie; Andreasen, Jakob Nørgaard; Olsen, Jens

    2016-08-01

    Objectives Currently, patients with persistent moderate-to-severe house dust mite (HDM) allergic rhinitis despite use of symptom-relieving medication can be offered subcutaneously administered allergy immunotherapy (SQ SCIT; Alutard SQ) as standard care of treatment in Denmark. Recently, a HDM sublingually administered allergy immunotherapy tablet (SQ SLIT-tablet; ACARIZAX) has been developed for at-home treatment. The purpose of this analysis is to compare the costs related to treatment and administration of SQ SLIT-tablet and SQ SCIT. Methods Assuming equal efficacy between ther SQ SLIT-tablet and SQ SCIT, the cost-minimization analysis was the most appropriate for the comparison. According to guidelines and Summary of Product Characteristics, the treatment duration of SQ SLIT-tablet is 3 years and 3-5 years for SQ SCIT. The courses of treatment vary among patients and, therefore, the costs of treatment have been calculated for an average patient with HDM respiratory allergic disease (RAD) receiving either SQ SLIT-tablet or SQ SCIT. All costs associated with allergy immunotherapy were collected, i.e., cost of medication, administration and treatment setting, and discounted according to Danish guidelines. Comprehensive univariate sensitivity analyses were carried out. Results The treatment costs for an average patient with HDM RAD are €3094 for SQ SLIT-tablet and €3799 for SQ SCIT; however, when adding indirect costs to the calculations the total costs of the treatments are €3697 and €6717 for SQ SLIT-tablet and SQ SCIT, respectively. Therefore, if 2500 patients with HDM RAD were treated with SQ SLIT-tablet instead of SQ SCIT, it would elicit a saving to the healthcare system of ∼€1.8 million. The conclusion was robust to any changes in the sensitivity analysis. Conclusion With regards to the cost of treating Danish patients with HDM RAD, it is clearly cost-saving to treat patients with SQ SLIT-tablet compared to SQ SCIT.

  5. The Effect of a Payer-Mandated Decrease in Buprenorphine Dose on Aberrant Drug Tests and Treatment Retention Among Patients with Opioid Dependence.

    Science.gov (United States)

    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

  6. Sublingual Immunotherapy for Allergic Fungal Sinusitis.

    Science.gov (United States)

    Melzer, Jonathan M; Driskill, Brent R; Clenney, Timothy L; Gessler, Eric M

    2015-10-01

    Allergic fungal sinusitis (AFS) is a condition that has an allergic basis caused by exposure to fungi in the sinonasal tract leading to chronic inflammation. Despite standard treatment modalities, which typically include surgery and medical management of allergies, patients still have a high rate of recurrence. Subcutaneous immunotherapy (SCIT) has been used as adjuvant treatment for AFS. Evidence exists to support the use of sublingual immunotherapy (SLIT) as a safe and efficacious method of treating allergies, but no studies have assessed the utility of SLIT in the management of allergic fungal sinusitis. A record review of cases of AFS that are currently or previously treated with sublingual immunotherapy from 2007 to 2011 was performed. Parameters of interest included serum IgE levels, changes in symptoms, Lund-McKay scores, decreased sensitization to fungal allergens associated with AFS, and serum IgE levels. Ten patients with diagnosed AFS were treated with SLIT. No adverse effects related to the use of SLIT therapy were identified. Decreases in subjective complaints, exam findings, Lund-McKay scores, and serum IgE levels were observed. Thus, sublingual immunotherapy appears to be a safe adjunct to the management of AFS that may improve patient outcomes. © The Author(s) 2015.

  7. Sublingual vitamin B12 compared to intramuscular injection in patients with type 2 diabetes treated with metformin: a randomised trial.

    Science.gov (United States)

    Parry-Strong, Amber; Langdana, Fali; Haeusler, Sylvan; Weatherall, Mark; Krebs, Jeremy

    2016-06-10

    MAIM: To compare a single 1mg intramuscular hydroxocobalamin injection with a 3-month course of 1mg/day sublingual methylcobalamin supplements on serum vitamin B12 concentrations in participants withtype 2 diabetes treated with metformin. Participants on metformin treatment with vitamin B12 concentrations below 220pmol/L were recruited through hospital diabetes clinics and primary care practices. They were randomised to receive either the injection or sublingual treatment. The primary outcome was serum vitamin B12 level after 3 months adjusted for baseline assessed by analysis of covariance (ANCOVA). The trial was registered on the Australia New Zealand Clinical Trial registry (ACTRN12612001108808). A total of 34 participants were randomised; 19 to the tablet, and 15 to the injection. The mean (SD) age, duration of diabetes, and duration of metformin use were, 64.2 (7.3) years, 13.7 (6.4) years, and 11.6 (5.0) years, respectively. After 3 months, the mean (SD) vitamin B12 was 372.1 (103.3) pmol/L in the tablet group (n=19) compared to 251.7 (106.8) pmol/L in the injection group (n=15), ANCOVA estimated difference -119.4 (95% CI -191.2 to -47.6), p=0.002. After 6 months, the mean (SD) serum B12 was 258.8 (58.7) pmol/L in the tablet group (n=17) and 241.9 (40.1) pmol/L in the injection group (n=15); ANCOVA estimated difference -15.2 (95% CI -50.3 to 19.8), p=0.38. Higher metformin dose was associated with lower serum B12 at 3 months, but not at baseline or 6 months. Decreased serum vitamin B12 level in patients with type 2 diabetes who are treated with metformin can be corrected through treatment with either hydroxocobalamin injections or methylcobalamin sublingual supplements.

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

    Science.gov (United States)

    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.

  9. 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 ...

  10. [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.

  11. 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...

  12. 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.

  13. 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

  14. Dust Mite-Induced Perennial Allergic Rhinitis in Pediatric Patients and Sublingual Immunotherapy.

    Science.gov (United States)

    Anderson, Halie M; Wood, Robert A; Busse, William W

    Allergic rhinitis (AR) is a common illness in children and can impair their quality of life. Furthermore, many children remain symptomatic despite maximizing systemic antihistamine and topical therapies. It is at this clinical juncture that immunotherapy may be considered. The efficacy and safety associated with both subcutaneous (SCIT) and sublingual (SLIT) approaches are reviewed and positioned as treatment options for pediatric patients, with specific focus on current literature as it relates to SLIT in children, including those with perennial allergic rhinitis. Although there is more extensive experience with SLIT treatment in Europe, grass and ragweed tablet forms of SLIT are approved in the US. Approaches to the care of pediatric patients with allergic rhinitis are presented. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  15. 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

  16. 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

  17. Warfarin induced sublingual hematoma: a Ludwig angina mimic.

    Science.gov (United States)

    Pathak, Ranjan; Supplee, Suzanne; Aryal, Madan Raj; Karmacharya, Paras

    2015-01-01

    Sublingual hematoma is a rare but life-threatening complication of oral anticoagulants. It is important to differentiate this from infectious processes like Ludwig's angina. Securing the airway should be a priority and immediate reversal of anticoagulation with close monitoring is required. We present a case of sublingual hematoma secondary to warfarin therapy without airway compromise which was managed conservatively with reversal of INR with oral vitamin K. Although rare, it is crucial to differentiate sublingual hematomas from infectious processes. Reversal of anticoagulation with low threshold for artificial airway placement in the event of airway compromise is the treatment of choice. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Network meta-analysis shows commercialized subcutaneous and sublingual grass products have comparable efficacy.

    Science.gov (United States)

    Nelson, Harold; Cartier, Shannon; Allen-Ramey, Felicia; Lawton, Simon; Calderon, Moises A

    2015-01-01

    Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) have been shown to effectively treat grass pollen allergies, although direct comparisons are sparse. To estimate the relative efficacy of SLIT tablets compared with SCIT and SLIT drops in commercially available products though network meta-analysis. A literature search of MEDLINE, Embase, and Cochrane Library publications. Randomized, double-blind clinical trials of SCIT, SLIT drops, and SLIT tablets for grass pollen were included. Bayesian network meta-analyses estimated the standardized mean difference (SMD) across 3 immunotherapy modalities on allergic rhinoconjunctivitis symptom and medication score data from publications or received from authors. Both fixed and random effects models were investigated. Thirty-seven studies were included in meta-analyses for symptom scores and 31 studies for medication scores. In the random effects model, SCIT and SLIT tablets were significantly different from placebo for symptom scores: SMDs (95% CI) of -0.32 (-0.45 to -0.18) and -0.32 (-0.41 to -0.23), respectively. No significant difference was identified for SLIT drops compared with placebo (SMD, -0.17; -0.37 to 0.04). For medication scores, significant differences compared with placebo were observed for SCIT (SMD, -0.33; 95% CI, -0.52 to -0.13), SLIT tablets (SMD, -0.23; 95% CI, -0.29 to -0.17), and SLIT drops (SMD, -0.44; 95% CI, -0.83 to -0.06). Network meta-analysis revealed no significant differences in SMDs (95% credible interval) for symptom scores (0.0145 [-0.19 to 0.23]) or medication scores (0.133 [-0.31 to 0.57]) between SLIT tablets and SCIT, or for symptom scores (-0.175 [-0.37 to 0.02]) and medication scores (0.188 [-0.18 to 0.56]) between SLIT tablets and SLIT drops. The comparisons for grass pollen immunotherapy products commercialized in at least 1 country indicate comparable reductions in allergic rhinoconjunctivitis symptoms and supplemental medication use for SLIT tablets

  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. Gum pigmentation: an unusual adverse effect of sublingual immunotherapy

    OpenAIRE

    Goh, Anne; Chiang, Wen Chin; Kang, Liew Woei; Rao, Rajeshwar; Lim, Hwee Hoon; Chng, Chai Kiat

    2014-01-01

    Sublingual immunotherapy has gained acceptance amongst the paediatric community as it is very well tolerated and is safe. The adverse effects of this therapy is minimal consisting mainly of local side effects within the oral cavity such as itching of the mouth, swelling of the lips and less frequently abdominal pain, wheezing and urticaria has been described. This report is to highlight another local side effect of sublingual immunotherapy which has been observed in 3 of our patients. This is...

  1. Same effect of sublingual and oral captopril in hypertensive crisis.

    Science.gov (United States)

    Karakiliç, E; Büyükcam, F; Kocalar, G; Gedik, S; Atalar, E

    2012-11-01

    Hypertensive crisis is a condition characterized by rapid and inappropriate symptomatic elevation of blood pressure (BP) that is commonly seen in Emergency Departments. Oral or sublingual captopril is commonly used in the Emergency Departments. The unpleasant taste of the sublingual drugs causes uncomfortable condition to the patient. Studies showing no difference between oral and sublingual captopril has been ignored so far. Herein we compared the oral and sublingual captopril efficiency in the hypertensive urgencies. In this retrospective observational study, 71 patients admitted with hypertensive urgency to Emergency Departments of two hospitals in 2011 whose blood pressure were recorded before captopril administration and blood pressure were recorded after captopril administration at 0-5-15-30-45-60 minutes were included the study. The reductions of the blood pressure of oral and sublingual captopril groups were compared. There were 28 patients at oral and 43 at sublingual captopril group. The mean age ± SD was 58.13 ± 8.66 years and 41 (57.7%) patients were female. The most common complaints were headache, nausea/vomiting and weakness. 65 (91.5%) patients were using antihypertensive drugs before admitted to hospital. The blood pressure at 0, 5, 15, 30, 45 and 60th minutes of therapy didn't show any difference between oral and sublingual captopril use. There was any difference between oral and sublingual captopril efficiency to control of hypertension in patient with hypertensive urgency. For a more comfortable treatment, oral captopril may be a more convenient choice in the hypertensive urgencies.

  2. Debut of Gastroesophageal Reflux Concomitant with Administration of Sublingual Immunotherapy

    DEFF Research Database (Denmark)

    Juel, J.

    2017-01-01

    , and dysphagia. Sublingual immunotherapy (SLIT) was first described in 1986. Following this description, the use has greatly increased in the treatment of allergic rhinitis, as an alternative to subcutaneously administered immunotherapy. Side effects are commonly of oropharyngeal and gastrointestinal nature...... to administration of sublingual immunotherapy for house dust mite in allergic rhinitis. The patient had to stop the SLIT after two weeks of administration due to GORD. The cessation resulted in rapid resolution of symptoms....

  3. Sublingual immunotherapy: World Allergy Organization position paper 2013 update

    Science.gov (United States)

    2014-01-01

    We have prepared this document, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update”, according to the evidence-based criteria, revising and updating chapters of the originally published paper, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2009”, available at http://www.waojournal.org. Namely, these comprise: “Mechanisms of sublingual immunotherapy;” “Clinical efficacy of sublingual immunotherapy” – reporting all the data of all controlled trials published after 2009; “Safety of sublingual immunotherapy” – with the recently published Grading System for adverse reactions; “Impact of sublingual immunotherapy on the natural history of respiratory allergy” – with the relevant evidences published since 2009; “Efficacy of SLIT in children” – with detailed analysis of all the studies; “Definition of SLIT patient selection” – reporting the criteria for eligibility to sublingual immunotherapy; “The future of immunotherapy in the community care setting”; “Methodology of clinical trials according to the current scientific and regulatory standards”; and “Guideline development: from evidence-based medicine to patients' views” – including the evolution of the methods to make clinical recommendations. Additionally, we have added new chapters to cover a few emerging crucial topics: “Practical aspects of schedules and dosages and counseling for adherence” – which is crucial in clinical practice for all treatments; “Perspectives and new approaches” – including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, “Raising public awareness about sublingual immunotherapy”, as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail. PMID:24679069

  4. NUT Carcinoma of the Sublingual Gland

    DEFF Research Database (Denmark)

    Andreasen, Simon; French, C A; Josiassen, Michael

    2016-01-01

    NUT carcinoma (NC) is a recently described, rare and extremely aggressive cancer primarily located to supradiaphragmatic structures and affecting young individuals. NC is characterized by translocations involving the NUT gene on 15q14 with the most common translocation partner gene being BRD4 on 19......p13, resulting in the t(15;19)(q14;p13) karyotype. NC is poorly differentiated and is likely to be overlooked and misdiagnosed as poorly differentiated squamous cell carcinoma (SCC) when immunohistochemical evaluation of NUT protein expression is omitted. Previously, NC has been found in the parotid...... and submandibular glands and we present the first case in the sublingual gland arising in a 40-year-old woman. We discuss the diagnostic considerations for poorly differentiated carcinomas of the salivary glands and advocate the inclusion of NUT immunohistochemistry in this setting. Not only does the NC diagnosis...

  5. 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.

  6. Effect of Two Years of Treatment with Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at Three Years among Patients with Moderate to Severe Seasonal Allergic Rhinitis: A Randomized Clinical Trial

    Science.gov (United States)

    Scadding, Guy W.; Calderon, Moises A.; Shamji, Mohamed H.; Eifan, Aarif O.; Penagos, Martin; Dumitru, Florentina; Sever, Michelle L.; Bahnson, Henry T; Lawson, Kaitie; Harris, Kristina M.; Plough, Audrey G.; Panza, Joy Laurienzo; Qin, Tielin; Lim, Noha; Tchao, Nadia K.; Togias, Alkis; Durham, Stephen R.

    2017-01-01

    Importance Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least two years following discontinuation of treatment. Objective To assess whether 2 years of treatment with grass pollen sublingual immunotherapy compared with placebo provides improved nasal response to allergen challenge at 3 year follow-up. Design, Setting, Participants A randomized double-blind, placebo-controlled, 3-parallel group study performed in a single academic centre, Imperial College London, including adult patients with moderate-to-severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrolment was March 2011, last follow-up February 2015. Intervention Thirty-six participants received 2 years sublingual immunotherapy (daily tablets containing 15 microgram of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 micrograms of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years and at 3 years (1 year after treatment discontinuation). Main outcomes and measures Total nasal symptom scores (TNSS, range 0 (best) to 12 (worst) were recorded during 0–10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy to placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. Results Among 106 participants who were randomized (mean age 33.5 years, 32.1% female), 92 completed the study at 3 years. Imputed TNSS scores [mean (95% confidence intervals)] pre-treatment and

  7. Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis: The GRASS Randomized Clinical Trial.

    Science.gov (United States)

    Scadding, Guy W; Calderon, Moises A; Shamji, Mohamed H; Eifan, Aarif O; Penagos, Martin; Dumitru, Florentina; Sever, Michelle L; Bahnson, Henry T; Lawson, Kaitie; Harris, Kristina M; Plough, Audrey G; Panza, Joy Laurienzo; Qin, Tielin; Lim, Noha; Tchao, Nadia K; Togias, Alkis; Durham, Stephen R

    2017-02-14

    Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment. To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up. A randomized double-blind, placebo-controlled, 3-parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015. Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation). Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5

  8. Sublingual ketorolac and sublingual piroxicam are equally effective for postoperative pain, trismus, and swelling management in lower third molar removal.

    Science.gov (United States)

    Trindade, Paulo A K; Giglio, Fernando P M; Colombini-Ishikiriama, Bella L; Calvo, Adriana M; Modena, Karin Cristina S; Ribeiro, Debora A; Dionísio, Thiago J; Brozoski, Daniel T; Lauris, José Roberto P; Faria, Flávio Augusto C; Santos, Carlos F

    2012-07-01

    Lower third molar removal provides a clinical model for studying analgesic drugs. The present study's aim was to compare the clinical efficacy of sublingual ketorolac and sublingual piroxicam in managing pain, trismus and swelling after lower third molar extraction in adult volunteers. In this double-blinded, randomized, crossover investigation, 47 volunteers received for 4 days ketorolac sublingually (10 mg 4 times daily) and piroxicam sublingually (20 mg once daily) during 2 separate appointments after lower third molar extraction of symmetrically positioned lower third molars. A surgeon evaluated objective parameters (surgery duration, mouth opening, rescue analgesic medication, and facial swelling) and volunteers documented subjective parameters (postoperative pain and global evaluation), comparing postoperative results for a total of 7 days after surgery. The means of the objective and subjective parameters were compared for statistical significance (P .05). Additionally, values for mouth openings measured just before surgery and immediately after suture removal 7 days later were similar among volunteers (P > .05), and the type of nonsteroidal antiinflammatory drug (NSAID) used in this study showed no significant differences between swellings on the second or seventh days after surgery (P > .05). Pain, trismus, and swelling after lower third molar extraction, independent of surgical difficulty, were successfully controlled by sublingual ketorolac (10 mg 4 times daily) or sublingual piroxicam (20 mg once daily), and no significant differences were observed between the NSAIDs evaluated. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Long-term safety and analgesic efficacy of buprenorphine buccal film in patients with moderate-to-severe chronic pain requiring around-the-clock opioids

    Directory of Open Access Journals (Sweden)

    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

  10. 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.

  11. 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 ...

  12. 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.

  13. 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.

  14. Enhanced efficacy of sublingual immunotherapy by liposome-mediated delivery of allergen

    DEFF Research Database (Denmark)

    Aliu, Have; Rask, Carola; Brimnes, Jens

    2017-01-01

    Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the - treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development...

  15. 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.

  16. Tablet Use within Medicine

    Science.gov (United States)

    Hogue, Rebecca J.

    2013-01-01

    This paper discusses the scholarly literature related to tablet computer use in medicine. Forty-four research-based articles were examined for emerging categories and themes. The most studied uses for tablet computers include: patients using tablets to complete diagnostic survey instruments, medical professionals using tablet computers to view…

  17. 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.

  18. Sublingual sufentanil, a new opportunity for the improvement of postoperative pain management in Italy.

    Science.gov (United States)

    Sacerdote, P; Coluzzi, F; Fanelli, A

    2016-04-01

    Despite the availability of national and international guidelines, adequate postoperative pain (POP) management is still a challenge in Italy. One of the potential reasons for the high incidence of surgical patients complaining moderate to severe pain is the difficult application of the currently recommended analgesic techniques in clinical practice. In particular, morphine, the most commonly used systemic opioid in the POP treatment, has some unfavorable pharmacodynamic and pharmacokinetic characteristics for POP management, suggesting a potential relevant improvement by using different opioids. Many of sufentanil properties make it particularly suitable for POP control: a high affinity for the µ opioid receptor, the highest therapeutic index compared to any other opioid used in clinical practice and the absence of clinically relevant active metabolites. The elevated potency, together with the high lipophilicity of sufentanil, allow the preparation of a nanotablet, 3 mm of diameter and 0.75 mm of thickness, containing 15 µg of active drug. The sublingual route allows a longer time of drug plasmatic permanence in comparison to IV route, overcoming the need for continuous dosing. The patient-controlled system, considered in the present review, is preprogrammed to deliver one sublingual tablet of sufentanil with a 20-minute lockout period with a radiofrequency identification thumb tag allowing only the patient to activate the on demand button. Phase II and III studies have assessed the efficacy of this system in POP management, showing that it was considered more satisfactory than the IV PCA morphine system by both patients and nurses. The introduction of this simple and innovative system of patient-controlled analgesic administration could represent an opportunity for Italy to update the current practice in POP management.

  19. 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.

  20. Sublingual Immunotherapy in Children: An Updated Review

    Directory of Open Access Journals (Sweden)

    Chang-Hung Kuo

    2009-04-01

    Full Text Available Although pharmacological therapy and allergen avoidance are effective means of managing allergic disease, allergen-specific immunotherapy is able to treat not only the symptoms, but also the underlying causes of the disease. Sublingual immuno-therapy (SLIT has been shown to be effective in patients with allergic diseases. It has demonstrated long-term clinical benefits and shown the potential to modify the course of allergic disease in children with rhinitis, conjunctivitis, and asthma. The precise mechanisms of SLIT remain unclear, but antigen-presenting cells in the oral mucosa may induce regulatory T-cells that suppress the allergic immune response by increasing production of interleukin-10. SLIT has also been shown to increase allergen-specific IgG antibodies that antagonize and block the allergic response. SLIT was well tolerated in all reported, double-blinded, placebo-controlled, randomized trials. SLIT is an ideal means of treating the pediatric population because of its excellent safety and good compliance. However, the optimal dose and duration of SLIT require further investigation.

  1. Sublingual Microcirculation is Impaired in Post-cardiac Arrest Patients

    DEFF Research Database (Denmark)

    G. Omar, Yasser; Massey, Michael; Wiuff Andersen, Lars

    2013-01-01

    the microcirculation flow index (MFI) at 6 and 24h in the cardiac arrest patients, and within 6h of emergency department admission in the sepsis and control patients. RESULTS: We evaluated 30 post-cardiac arrest patients, 16 severe sepsis/septic shock patients, and 9 healthy control patients. Sublingual...... markers in the post-cardiac arrest state. METHODS: We prospectively evaluated the sublingual microcirculation in post-cardiac arrest patients, severe sepsis/septic shock patients, and healthy control patients using Sidestream Darkfield microscopy. Microcirculatory flow was assessed using...

  2. 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 ...

  3. Pharmacokinetics of a novel sublingual spray formulation of the antimalarial drug artemether in African children with malaria.

    Science.gov (United States)

    Salman, Sam; Bendel, Daryl; Lee, Toong C; Templeton, David; Davis, Timothy M E

    2015-01-01

    The pharmacokinetics of sublingual artemether (ArTiMist) was investigated in 91 young African children with severe malaria or who could not tolerate oral antimalarial therapy. Each received 3.0 mg/kg of body weight of artemether at 0, 8, 24, 36, 48, and 60 h or until the initiation of oral treatment. Few blood samples were drawn postdose. Plasma artemether and dihydroartemisinin (DHA) levels were measured using liquid chromatography-mass spectrometry, and the data were analyzed using established population compartmental pharmacokinetic models. Parasite clearance was prompt (median parasite clearance time, 24 h), and there were no serious adverse events. Consistent with studies in healthy adults (S. Salman, D. Bendel, T. C. Lee, D. Templeton, and T. M. E. Davis, Antimicrob Agents Chemother 59:3197-3207, 2015, http://dx.doi.org/10.1128/AAC.05013-14), the absorption of sublingual artemether was biphasic, and multiple dosing was associated with the autoinduction of the metabolism of artemether to DHA (which itself has potent antimalarial activity). In contrast to studies using healthy volunteers, pharmacokinetic modeling indicated that the first absorption phase did not avoid first-pass metabolism, suggesting that the drug is transferred to the upper intestine through postdose fluid/food intake. Simulations using the present data and those from an earlier study in older Melanesian children with uncomplicated malaria treated with artemether-lumefantrine tablets suggested that the bioavailability of sublingual artemether was at least equivalent to that after conventional oral artemether-lumefantrine (median [interquartile range] areas under the concentration-time curve for artemether, 3,403 [2,471 to 4,771] versus 3,063 [2,358 to 4,514] μg · h/liter, respectively; and for DHA, 2,958 [2,146 to 4,278] versus 2,839 [1,812 to 3,488] μg · h/liter, respectively; P ≥ 0.42). These findings suggest that sublingual artemether could be used as prereferral treatment for sick

  4. 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.

  5. 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

  6. Sublingual lorazepam in the treatment of familial paroxysmal nonkinesigenic dyskinesia.

    Science.gov (United States)

    Dooley, Joseph M; Brna, Paula M

    2004-05-01

    Familial paroxysmal nonkinesigenic dyskinesia (Mount and Reback syndrome) is characterized by episodes of dystonia and chorea, which are precipitated by fatigue, emotional stress, alcohol, or foods. We report two children from a large kindred with this condition who responded to sublingual lorazepam.

  7. Abnormal blood flow in the sublingual microcirculation at high altitude

    NARCIS (Netherlands)

    Martin, Daniel S.; Ince, Can; Goedhart, Peter; Levett, Denny Z. H.; Grocott, Mike P. W.

    2009-01-01

    We report the first direct observations of deranged microcirculatory blood flow at high altitude, using sidestream dark-field imaging. Images of the sublingual microcirculation were obtained from a group of 12 volunteers during a climbing expedition to Cho Oyu (8,201 m) in the Himalayas.

  8. CONGENITAL SUBLINGUAL DERMOID CYST IN A NEONATE: A ...

    African Journals Online (AJOL)

    there is no embryologic link between the two lesions. The differential diagnosis of dermoid cysts of floor of mouth include ranula, thyroglossal duct cyst, cystic hygroma, sialolithiasis or infection of the sublingual and submandibular glands, acute infection or cellulitis of the floor of mouth, benign. Tumours (eg. lipoma, fibroma, ...

  9. Time Evolution of Sublingual Microcirculatory Changes in Recreational Marathon Runners.

    Science.gov (United States)

    Pranskunas, Andrius; Arstikyte, Justina; Pranskuniene, Zivile; Bernatoniene, Jurga; Kiudulaite, Inga; Vaitkaitiene, Egle; Vaitkaitis, Dinas; Brazaitis, Marius

    2017-01-01

    We aimed to evaluate changes in sublingual microcirculation induced by a marathon race. Thirteen healthy male controls and 13 male marathon runners volunteered for the study. We performed sublingual microcirculation, using a Cytocam-IDF device (Braedius Medical, Huizen, Netherlands), and systemic hemodynamic measurements four times: 24 hours prior to their participation in the Kaunas Marathon (distance: 41.2 km), directly after finishing the marathon, 24 hours after the marathon, and one week after the marathon. The marathon runners exhibited a higher functional capillary density (FCD) and total vascular density of small vessels at the first visit compared with the controls. Overall, we did not find any changes in sublingual microcirculation of the marathon runners at any of the other visits. However, in a subgroup of marathon runners with a decreased FCD compared to the subgroup with increased FCD, the subgroup with decreased FCD had shorter running time (190.37 ± 30.2 versus 221.80 ± 23.4 min, p = 0.045), ingested less fluids (907 ± 615 versus 1950 ± 488 mL, p = 0.007) during the race, and lost much more weight (-2.4 ± 1.3 versus -1.0 ± 0.8 kg, p = 0.041). Recreational marathon running is not associated with an alteration of sublingual microcirculation. However, faster running and dehydration may be crucial for further impairing microcirculation.

  10. Time Evolution of Sublingual Microcirculatory Changes in Recreational Marathon Runners

    Directory of Open Access Journals (Sweden)

    Andrius Pranskunas

    2017-01-01

    Full Text Available We aimed to evaluate changes in sublingual microcirculation induced by a marathon race. Thirteen healthy male controls and 13 male marathon runners volunteered for the study. We performed sublingual microcirculation, using a Cytocam-IDF device (Braedius Medical, Huizen, Netherlands, and systemic hemodynamic measurements four times: 24 hours prior to their participation in the Kaunas Marathon (distance: 41.2 km, directly after finishing the marathon, 24 hours after the marathon, and one week after the marathon. The marathon runners exhibited a higher functional capillary density (FCD and total vascular density of small vessels at the first visit compared with the controls. Overall, we did not find any changes in sublingual microcirculation of the marathon runners at any of the other visits. However, in a subgroup of marathon runners with a decreased FCD compared to the subgroup with increased FCD, the subgroup with decreased FCD had shorter running time (190.37±30.2 versus 221.80±23.4 min, p=0.045, ingested less fluids (907±615 versus 1950±488 mL, p=0.007 during the race, and lost much more weight (-2.4±1.3 versus -1.0±0.8 kg, p=0.041. Recreational marathon running is not associated with an alteration of sublingual microcirculation. However, faster running and dehydration may be crucial for further impairing microcirculation.

  11. Effects of Sublingual Captopril in Immediate Treatment of Hypertensive Crisis

    Directory of Open Access Journals (Sweden)

    H. Kazerani

    2007-04-01

    Full Text Available Introduction & Objective: Sublingual captopril was shown to be a safe and effective drug to control hypertensive urgencies. However the exact time and efficacy of lowering blood pressure (BP is a matter of interest and importance. In this study we evaluated the time and efficacy of 25 mg sublingual captopril in lowering blood pressure. Materials & Methods: In a randomized clinical trial 101 patients (34 men, 67 women with blood pressure of 180/110 mmHg (or more who had no finding of major organ damage (heart – brain -eyes –renal were studied by prescription of 25 mg sublingual captopril. Then systolic and diastolic blood pressure was measured at 5, 10, 15, 20, 25, 30, 40, 50, 60, 75, 90, 105, 120 minutes following drug administration. Data analysis was performed using paired t-test and SPSS software. Results: The results showed that almost all the patients had some decrease in BP. After 120 minutes blood pressure dropped about 5% in 30%, and 5-30% in 70% of patients, compared to first measured BP. Maximal effect was observed in 25-30 minutes after drug administration: after 30 minutes systolic pressure dropped in 68.4% and diastolic pressure in 65.3% of patients about 5-25%. 47 patients had low response to therapy after 60 minutes, so they received another 25 mg captopril sublingual, which BP dropped in 45% of them. 19 patients were prescribed IV furosemide after 120 minutes. This group had resistant HTN and 25 cases of them were treated with ACEI previously. BP decreased gradually and not more than 30% of first BP. None of the patients encountered side effects. Conclusion: Sublingual captopril is a good, safe, effective, available and cost effective drug, with very low side effects in treating patients with hypertensive crisis. It is recommended to use this drug instead of Nifedipine in all hypertensive patients.

  12. 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.

  13. Fast-Acting Sublingual Zolpidem for Middle-of-the-Night Wakefulness

    Directory of Open Access Journals (Sweden)

    Joseph V. Pergolizzi

    2014-01-01

    Full Text Available Sleep disorders (somnipathies are conditions characterized by disruptions of sleep quality or of sleep pattern. They can involve difficulty falling asleep (prolonged sleep onset latency, difficulty staying asleep (disturbance of sleep maintenance, sleep of poor quality (unrefreshing, or combinations of these and can lead to poor health and quality of life problems. A subtype of sleep-maintenance insomnia is middle-of-the-night wakefulness, a relatively common occurrence. Zolpidem, a nonbenzodiazepine benzodiazepine receptor agonist, allosterically modulates an ion channel and increases the influx of Cl−, thereby dampening the effect of excitatory (sleep disrupting input. Recently, product label changes to some zolpidem containing products have been implemented by the FDA in order to reduce the risk associated with their morning after residual side effects. A new formulation of zolpidem tartrate (Intermezzo sublingual tablet, an approved product indicated exclusively for the treatment of middle-of-the-night wakefulness and difficulty returning to sleep, did not have its label changed. We present a short summary of its basic science and clinical attributes in light of the recent regulatory changes for zolpidem products.

  14. 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

  15. 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

  16. A Retrospective Cohort Study of Birth Outcomes in Neonates Exposed to Naltrexone in Utero: A Comparison with Methadone-, Buprenorphine- and Non-opioid-Exposed Neonates.

    Science.gov (United States)

    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

  17. Ação do mononitrato-5 de isossorbida sublingual durante cinecoronariografia. Comparação com o uso de nitroglicerina sublingual Sublingual isosorbide-5 mononitrate during coronary arteriography. Comparison with sublingual nitroglycerin

    Directory of Open Access Journals (Sweden)

    Anellys E. L. C. Moreira

    1997-10-01

    Full Text Available OBJETIVO: Avaliar o efeito sublingual do mononitrato-5 de isossorbida (MN5IS e nitroglicerina (NTG sobre o diâmetro luminal de artérias coronárias epicárdicas, pressão arterial média e efeitos colaterais. MÉTODOS: Cinqüenta pacientes foram submetidos a cateterismo cardíaco e cinecoronariografia, na condição inicial e 5min após administração sublingual de MN5IS grupo A (GA ou NTG grupo B (GB. RESULTADOS: O diâmetro coronário de referência aumentou em ambos os grupos, sem significância estatística entre os mesmos. Nos GA e GB foram demonstrados uma diminuição (1,66mmHg e um aumento (0,79mmHg na pressão arterial média, respectivamente (p=0,123. Não foram observados efeitos colaterais com o uso destas drogas. CONCLUSÃO: MN5IS sublingual é uma alternativa à administração de NTG durante cinecoronariografia e representa uma alternativa terapêutica para o tratamento de doença cardíaca isquêmica.PURPOSE: To evaluate the effect of sublingual isosorbide-5 mononitrate (ISMN and nitroglycerin (NTG on luminal diameter of epicardial coronary arteries, mean arterial pressure and deleterious effects. METHODS: Fifty patients were submitted to cardiac catheterization and coronary arteriography, at baseline, and 5min after sublingual administration of ISMN, group A (GA or NTG, group B (GB. RESULTS: Reference vessel diameter increased in both groups, without statistical significance. In GA and GB, a decrease (1.66mmHg and an increase (0.79mmHg in mean arterial pressure, respectively, were demonstrated (p=0.123. There were no deleterious effects with the use of these drugs. CONCLUSION: Sublingual ISMN is an alternative to administration of NTG during coronary arteriography, and represents a therapeutic alternative to ischemic heart disease treatment.

  18. Sublingual immunotherapy provides long-term relief in allergic rhinitis and reduces the risk of asthma: A retrospective, real-world database analysis.

    Science.gov (United States)

    Zielen, S; Devillier, P; Heinrich, J; Richter, H; Wahn, U

    2018-01-01

    Allergy immunotherapy (AIT) is the only treatment for allergic rhinitis (AR) and/or allergic asthma (AA) with long-term efficacy. However, there are few real-life data on the progression of AR and/or AA in patients receiving AIT. To assess the real-world, long-term efficacy of grass pollen sublingual immunotherapy (SLIT) tablets in AR and their impact on asthma onset and progression. In a retrospective analysis of a German longitudinal prescription database, AR patients treated with grass pollen SLIT tablets were compared with a control group not having received AIT. Multiple regression analysis was used to compare changes over time in rescue symptomatic AR medication use after treatment cessation, asthma medication use, and the time to asthma onset in the two groups. After applying all selection criteria, 2851 SLIT and 71 275 control patients were selected for the study. After treatment cessation, AR medication use was 18.8 percentage points lower (after adjustment for covariates, and relative to the pretreatment period) in SLIT tablet group than in the non-AIT group (PReal-world treatment of AR patients with grass pollen SLIT tablets was associated with slower AR progression, less frequent asthma onset, and slower asthma progression. © 2017 The Authors. Allergy Published by John Wiley & Sons Ltd.

  19. Comparison of sublingual and vaginal misoprostol for second-trimester pregnancy terminations.

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    Forozan Milani

    2014-03-01

    Full Text Available Comparing sublingual and vaginal misoprostol in second trimester pregnancy termination.In this study 268 women at 12-24 weeks of gestation candidate for pregnancy termination were enrolled. Women were randomly divided in two groups. The first group received 400 µg sublingual misoprostol and vaginal placebo and the second group received 400 µg vaginal misoprostol and sublingual placebo every 4 hours for a maximum of five doses. The course of misoprostol was repeated if the women did not abort within 24 hours.The median induction-to-abortion interval was shorter in sublingual group (12/72 hours in sublingual and 14/67 hours in vaginal. There was no significant difference in the success rate at 24 and 48 hours and in side effects. The preference for the sublingual route of administration was higher.Both vaginal and sublingual misoprostol are effective for medical abortion in second trimester termination. But it appears from shorter induction interval in sublingual and higher acceptability that sublingual route is a better choice.

  20. Gum pigmentation: an unusual adverse effect of sublingual immunotherapy.

    Science.gov (United States)

    Goh, Anne; Chiang, Wen Chin; Kang, Liew Woei; Rao, Rajeshwar; Lim, Hwee Hoon; Chng, Chai Kiat

    2014-07-01

    Sublingual immunotherapy has gained acceptance amongst the paediatric community as it is very well tolerated and is safe. The adverse effects of this therapy is minimal consisting mainly of local side effects within the oral cavity such as itching of the mouth, swelling of the lips and less frequently abdominal pain, wheezing and urticaria has been described. This report is to highlight another local side effect of sublingual immunotherapy which has been observed in 3 of our patients. This is pigmentation of the gums which can occur anytime during the course of the immunotherapy. It resolves on stopping the immunotherapy and is likely due to a local inflammatory process occurring in the gums of these children. There is no associated pain or itching with the pigmentation. It can persist as long as the child is on the immunotherapy.

  1. Therapeutic Effects and Biomarkers in Sublingual Immunotherapy: A Review

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    Takashi Fujimura

    2012-01-01

    Full Text Available Immunotherapy is considered to be the only curative treatment for allergic diseases such as pollinosis, perennial rhinitis, asthma, and food allergy. The sublingual route is widely applied for immunotherapy for allergy, instead of the conventional administration by subcutaneous route. A recent meta-analysis of sublingual immunotherapy (SLIT has shown that this approach is safe, has positive clinical effects, and provides prolonged therapeutic effects after discontinuation of treatment. However, the mechanism of SLIT and associated biomarkers are not fully understood. Biomarkers that change after or during SLIT have been reported and may be useful for response monitoring or as prognostic indicators for SLIT. In this review, we focus on the safety, therapeutic effects, including prolonged effects after treatment, and new methods of SLIT. We also discuss response monitoring and prognostic biomarkers for SLIT. Finally, we discuss immunological mechanisms of SLIT with a focus on oral dendritic cells and facilitated antigen presentation.

  2. 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.

  3. A Cost-Minimisation Analysis Comparing Sublingual Immunotherapy to Subcutaneous Immunotherapy for the Treatment of House Dust Mite Allergy in a Swedish Setting.

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    Björstad, Åse; Cardell, Lars-Olaf; Hahn-Pedersen, Julie; Svärd, Mikael

    2017-06-01

    In Sweden, approximately 6% of children and 10% of adults suffer from house dust mite (HDM) allergy with symptoms of allergic rhinitis and allergic asthma. Treatment is aimed at reducing HDM exposure and to control the symptoms of allergic rhinitis and allergic asthma by symptom-relieving pharmacotherapy. This pharmacotherapy is often effective, but some patients remain inadequately controlled. For these patients, allergy immunotherapy (AIT, subcutaneous or sublingual) with repeated administration of HDM allergen should be considered. The objective of this study was to compare the costs for sublingual AIT (SLIT; SQ® SLIT-tablet) to the costs for subcutaneous AIT (SCIT; SQ® SCIT) for the treatment of HDM allergy in a cost-minimisation analysis (CMA). The CMA included resources (and costs) for treatment, healthcare visits, travelling and lost productivity. Resource use based on Swedish clinical treatment practice and costs were obtained from medical price lists. Analyses were conducted from the societal, as well as healthcare perspective, by use of a time horizon of 3 years. The results show that SQ® SLIT-tablet is a cost-saving treatment as compared to SQ® SCIT for the treatment of HDM allergy (€6800 over 3 years). The results are mainly driven by the cost of healthcare visits and the frequency of SCIT administrations. In conclusion, cost-savings of €6800 over 3 years are expected from treating HDM allergy with SQ® SLIT-tablet as compared to SQ® SCIT, including costs for treatment, healthcare visits, travelling and lost productivity. The reduced number of healthcare visits compensates for higher medication costs.

  4. Current issues on sublingual allergen-specific immunotherapy in children with asthma and allergic rhinitis

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    Živković Zorica

    2016-01-01

    Full Text Available In 1993 the European Academy of Allergy and Clinical Immunology was the first official organization to recognize that sublingual administration could be “promising route” for allergic desensitization. A few years later, the World Health Organization recommended this therapy as “a viable alternative to the injection route in adults.” The first meta-analysis showed sublingual allergen specific immunotherapy (SLIT effectiveness for allergic rhinitis and another study showed SLIT can actually help prevent the development of asthma both in adults and in children. The main goal of this review article is to present insight into the most up-to-date understanding of the clinical efficacy and safety of immunotherapy in the treatment of pediatric patients with allergic rhinitis and asthma. A literature review was performed on PubMed from 1990 to 2015 using the terms “asthma,” “allergic rhinitis,” “children,” “allergen specific immune therapy.” Evaluating data from double-blind placebo-controlled randomized clinical trials (DB-PC-RCTs, the clinical efficacy (assessed as the reduction of symptom score and the need of rescue medicament of SLIT for allergic rhinitis and allergic asthma, has been confirmed in various meta-analysis Outcomes such as rhinoconjunctivitis score and medication scores, combined scores, quality of life, days with severe symptoms, immunological endpoints, and safety parameters were all improved in the SLIT-tablet compared with placebo group. SLIT safety has been already proven in many DB-PC-RCTs and real-life settings. In accordance with all of the above mentioned, the goals for future trials and studies are the development of comprehensive guidelines for clinical practice on immunotherapy, embracing all the different potential participants. The importance of allergen immunotherapy is of special relevance in the pediatric age, when the plasticity and modulability of the immune system are maximal, and when

  5. Sublingual immunotherapy for pediatric allergic rhinitis: The clinical evidence

    OpenAIRE

    Poddighe, Dimitri; Licari, Amelia; Caimmi, Silvia; Marseglia, Gian Luigi

    2016-01-01

    Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient’s daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure...

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Intranasal and sublingual delivery of inactivated polio vaccine.

    Science.gov (United States)

    Kraan, Heleen; Soema, Peter; Amorij, Jean-Pierre; Kersten, Gideon

    2017-05-09

    Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry. The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin. Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after

  16. 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.

  17. 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....

  18. 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...

  19. 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

  20. Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy

    DEFF Research Database (Denmark)

    Khinchi, M S; Poulsen, Lars K.; Carat, F

    2004-01-01

    Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed.......Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed....

  1. OF PARACETAMOL TABLETS

    African Journals Online (AJOL)

    compartmental analy- sis. The parameters for the uncoated ..... Drug absorption' from the uncoated tablets was fast and occurred _ over a relatively short period of time 'whilst ab- sorption from the film-coated tablets was slow and occurred over an extended ...

  2. A randomised comparison of oral desmopressin lyophilisate (MELT) and tablet formulations in children and adolescents with primary nocturnal enuresis

    DEFF Research Database (Denmark)

    Lottmann, H; Froeling, F; Alloussi, S

    2007-01-01

    AIMS: Desmopressin is a useful treatment for primary nocturnal enuresis (PNE), a common childhood condition that can persist into adolescence. This open-label, randomised, cross-over study evaluated the preference of children and adolescents with PNE for sublingual desmopressin oral lyophilisate...... for the MELT, and a statistically significant preference for desmopressin MELT in children aged 5-11 years. Desmopressin MELT had similar levels of efficacy and safety at lower dosing levels than the tablet, and therefore facilitates early initiation of PNE treatment in children aged 5-6 years. Udgivelsesdato.......88 +/- 1.94 bedwetting episodes/week; tablet: 1.90 +/- 1.85 episodes/week). Ease of use of both formulations was high. Compliance (> or = 80%) was 94.5% for MELT patients vs. 88.9% for the tablet (p = 0.059). No serious/severe adverse events were reported. CONCLUSIONS: There was an overall preference...

  3. Development of a Report Card for Identifying Local Sublingual Immunotherapy Events in Clinical Trials.

    Science.gov (United States)

    Norquist, Josephine; Flood, Emuella; Tanzosh, Tiffany; Li, Haojie; Iskold, Beata; Ganser, Thelma Rose; Marson-Smith, Helen

    2017-08-01

    The sublingual immunotherapy (SLIT) Report Card was developed to capture patient-reported local reactions from the administration of SLIT, based on the World Allergy Organization side-effect grading system. The objective was to evaluate understandability, usability, and translatability of the paper and electronic versions of the SLIT Report Card. Adults (aged 18+ years), adolescents (aged 12-17 years), and parents/caregivers and their children (aged 5-11 years) participated in two rounds of interviews, testing the paper version in Round 1, and both the paper and electronic versions in Round 2. Interviews assessed comprehension and usability by subjects. Translatability identified potential issues related to translation or cultural relevance. Ten adults, ten adolescents, and ten parent/child dyads were interviewed. In general, subjects demonstrated a clear understanding of the instrument's content. However, some subjects were uncertain of or suggested clarifying the meaning of certain terms, including tablet, ulcer, taste alteration, uvula, nausea, and itching in the ear. The translatability assessment also identified uvula and nausea as potentially problematic for translation. Subjects could use the electronic device and found navigation 'easy', with only a few minor suggestions made to improve usability. Some wording and formatting changes were made based on subjects' feedback and the translatability assessment. The SLIT Report Card was refined following best practices for instrument development, including cognitive interviewing, usability, and translatability assessment. The refined SLIT Report Card is appropriate for comprehensively and systematically collecting SLIT-related local reactions directly from subjects in a clinical trial setting, taking into account the World Allergy Organization grading system.

  4. Development of nanoparticle based delivery systems for sublingual immunotherapy

    DEFF Research Database (Denmark)

    Alija, Hava; Rask, Carola; Brimnes, Jens

    The prevalence of IgE mediated allergic diseases is increasing dramatically in industrialized countries. Sublingual immunotherapy (SLIT) has been demonstrated to be a safe and efficacious treatment for IgE mediated allergic diseases, but requires protracted treatment duration. Even though SLIT...... is considered to have a better safety profile than subcutaneous immunotherapy, SLIT can still cause adverse events requiring clinical supervision for the first administration. Optimization of SLIT, by reducing the administration dose and treatment duration, would improve safety profile. For this purpose...

  5. Android tablets for dummies

    CERN Document Server

    Gookin, Dan

    2015-01-01

    Learn all you need to know about your Android tablet in one quick and easy reference! It's not a computer and it's not a smartphone-so what in the world is it? Whether you're new to Android or new to tablets altogether, you're about to experience mobile computing like never before with this fun, full-color guide! Inside, longtime and bestselling author Dan Gookin walks you through setting up your Android tablet, navigating the interface, browsing the web, setting up email, connecting to social media, finding plenty of apps, music, books, and movies to indulge your interests-and so much more.

  6. 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.

  7. 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.

  8. 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....

  9. 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.

  10. 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.

  11. Sublingual vein parameters, AFP, AFP-L3, and GP73 in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Zhao, J; Guo, L-Y; Yang, J-M; Jia, J-W

    2015-06-26

    This study evaluated the diagnostic value of alpha-fetoprotein (AFP), AFP heterogeneity 3 (AFP-L3), Golgi protein 73 (GP73), and sublingual vein parameters in hepatocellular carcinoma (HCC). Levels of serum AFP, AFP-L3, GP73, and sublingual vein scores were measured in 34 patients with chronic hepatitis, 65 patients with post-hepatitis B cirrhosis, 71 patients with HCC, and 6 healthy controls. Logistic regression analysis was used to explore potential correlations. Sublingual vein grades in patients with HCC were higher than those in the other three groups; sublingual vein scores were also different between groups; combined diagnosis using AFP, GP73, and sublingual vein grade was superior to the individual parameters alone or when only two were used in different combinations. Thus, sublingual vein grade can be considered as an independent risk factor for diagnosis of HCC. Furthermore, combined detection with AFP, GP73, and sublingual vein grade is simple, inexpensive, and effective. It may therefore be suitable for screening high-risk populations for early diagnosis of HCC.

  12. Grasp interaction with tablets

    CERN Document Server

    Wolf, Katrin

    2015-01-01

    This book presents guidelines for a future device type: a tablet that allows ergonomic front- and back-of-device interaction. These guidelines help designers and developers of user interfaces to build ergonomic applications for tablet devices, in particular for devices that enable back-of-device interaction. In addition, manufacturers of tablet devices obtain arguments that back-of-device interaction is a promising extension of the interaction design space and results in increased input capabilities, enriched design possibilities, and proven usability. The guidelines are derived from empirical studies and developed to fit the users’ skills to the way the novel device type is held. Three particular research areas that are relevant to develop design guidelines for tablet interaction are investigated: ergonomic gestures, interaction areas, and pointing techniques.

  13. Tableting Properties and Compression Models of Labisia pumila Tablets.

    Science.gov (United States)

    Etti, C J; Yusof, Y A; Chin, N L; Mohd Tahir, S

    2017-03-04

    The tableting properties of Labisia pumila herbal powder, which is well known for its therapeutic benefits was investigated. The herbal powder was compressed into tablets using a stainless steel cylindrical uniaxial die of 13-mm- diameter with compaction pressures ranging from 7 to 25 MPa. Two feed weights, 0.5 and 1.0 g were used to form tablets. Some empirical models were used to describe the compressibility behavior of Labisia pumila tablets. The strength and density of tablets increased with increase in compaction pressure and resulted in reduction in porosity of the tablets. Smaller feeds, higher forces and increase in compaction pressure, contributed to more coherent tablets. These findings can be used to enhance the approach and understanding of tableting properties of Labisia pumila herbal powder tablets.

  14. Development of a sublingual allergy vaccine for grass pollinosis

    Directory of Open Access Journals (Sweden)

    Franco Frati

    2010-06-01

    Full Text Available Franco Frati1,2, Silvia Scurati1, Paola Puccinelli1, Marie David3, Cecile Hilaire4, Maurizio Capecce4, Francesco Marcucci2, Cristoforo Incorvaia51Medical and Scientific Department, Stallergenes, Milan, Italy; 2University Department of Medical and Surgical Specialties and Public Health, Perugia, Italy; 3Laboratoire Stallergenes, Antony, France; 4Marketing Department, Stallergenes, Milan, Italy; 5Allergy/Pulmonary Rehabilitation Unit, ICP Hospital, Milan, ItalyAbstract: Grass pollen is a very common cause of allergic rhinitis and asthma. The only treatment targeting the underlying causes of allergy is immunotherapy (IT. Sublingual immunotherapy (SLIT has been introduced to solve the problem of systemic reactions to subcutaneous IT (SCIT. This article evaluates the characteristics of the allergen extract, Staloral, in terms of practical administration, effectiveness, safety, and mechanism of action. Efficacy data were obtained from double-blind, placebo-controlled studies using Staloral in patients sensitized to grass pollen, while practical administration, cost-effectiveness, and mechanism of action data were provided by well designed studies. The efficacy and safety of Staloral, as demonstrated by review of published studies which used doses up to 1125 times those administered with SCIT, shows that this allergen extract has optimal characteristics for treating patients with seasonal allergies due to grass pollens. The main mechanism of action is the interaction between dendritic cells of the oral mucosa and the subsequent tolerance induced in T-cells.Keywords: allergen extracts, high-dose, efficacy, safety, sublingual immunotherapy

  15. 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...

  16. 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....

  17. A meta-analysis of sublingual allergen immunotherapy and pharmacotherapy in pollen-induced seasonal allergic rhinoconjunctivitis.

    Science.gov (United States)

    Devillier, Philippe; Dreyfus, Jean-François; Demoly, Pascal; Calderón, Moisés A

    2014-05-01

    The capacity of sublingual allergen immunotherapy (SLIT) to provide effective symptom relief in pollen-induced seasonal allergic rhinitis is often questioned, despite evidence of clinical efficacy from meta-analyses and well-powered, double-blind, placebo-controlled randomized clinical trials. In the absence of direct, head-to-head, comparative trials of SLIT and symptomatic medication, only indirect comparisons are possible. We performed a meta-analysis of classes of products (second-generation H1-antihistamines, nasal corticosteroids and grass pollen SLIT tablet formulations) and single products (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor antagonist montelukast) for the treatment of seasonal allergic rhinitis in adults, adolescents and/or children. We searched the literature for large (n >100 in the smallest treatment arm) double-blind, placebo-controlled randomized clinical trials. For each drug or drug class, we performed a meta-analysis of the effect on symptom scores. For each selected trial, we calculated the relative clinical impact (according to a previously published method) on the basis of the reported post-treatment or season-long nasal or total symptom scores: 100 × (scorePlacebo - scoreActive)/scorePlacebo. Twenty-eight publications on symptomatic medication trials and ten on SLIT trials met our selection criteria (total number of patients: n = 21,223). The Hedges' g values from the meta-analyses confirmed the presence of a treatment effect for all drug classes. In an indirect comparison, the weighted mean (range) relative clinical impacts were -29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, -17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and -6.5% (-3% to -10%) for montelukast. In an indirect comparison, grass pollen SLIT tablets had a greater mean relative clinical impact

  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. Concurrent Spontaneous Sublingual and Intramural Small Bowel Hematoma due to Warfarin Use

    Directory of Open Access Journals (Sweden)

    Gül Pamukçu Günaydın

    2015-01-01

    Full Text Available Introduction. We present a case of concurrent spontaneous sublingual and intramural small bowel hematoma due to warfarin anticoagulation. Case. A 71-year-old man presented to the emergency department complaining of a swollen, painful tongue. He was on warfarin therapy. Physical examination revealed sublingual hematoma. His international normalized ratio was 11.9. The computed tomography scan of the neck demonstrated sublingual hematoma. He was admitted to emergency department observation unit, monitored closely; anticoagulation was reversed with fresh frozen plasma and vitamin K. 26 hours after his arrival to the emergency department, his abdominal pain and melena started. His abdomen tomography demonstrated intestinal submucosal hemorrhage in the ileum. He was admitted to surgical floor, monitored closely, and discharged on day 4. Conclusion. Since the patient did not have airway compromise holding anticoagulant, reversing anticoagulation, close monitoring and observation were enough for management of both sublingual and spontaneous intramural small bowel hematoma.

  2. Parotid and submandibular/sublingual salivary flow during high dose radiotherapy

    NARCIS (Netherlands)

    Burlage, FR; Coppes, RP; Meertens, H; Stokman, MA; Vissink, A

    2001-01-01

    It was studied whether differences in acute radiosensitivity exist between parotid and submandibular/sublingual glands. The results revealed that salivary flow rates decreased dramatically during the first 2 weeks of radiotherapy. Neither recovery nor significant differences were observed between

  3. Critical appraisal of the clinical utility of sublingual immunotherapy in allergy

    Directory of Open Access Journals (Sweden)

    S. Aissa

    2016-12-01

    We performed a literature review in order to remind the mechanisms of action and to demonstrate efficacy and tolerability of the sublingual immunotherapy in the treatment of allergic rhinoconjunctivitis and asthma and its impact on the quality of life.

  4. Sublingual Nitroglycerin Administration in Coronary Computed Tomography Angiography : a Systematic Review

    NARCIS (Netherlands)

    Takx, Richard A. P.; Suchá, D.; Park, Jakob; Leiner, Tim; Hoffmann, Udo

    2015-01-01

    To systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography. A systematic

  5. effect of pre-operative sub-lingual misoprostol versus intravenous ...

    African Journals Online (AJOL)

    2012-09-09

    Sep 9, 2012 ... EFFECT OF PRE-OPERATIVE SUB-LINGUAL MISOPROSTOL VERSUS INTRAVENOUS OXYTOCIN ON CAESAREAN. OPERATION BLOOD LOSS ... infusion of oxytocin in reducing blood loss at Caesarean section operation. However, occurrence of ..... WHO Reproductive Health Library; Geneva: World.

  6. 3D Simulation of Internal Tablet Strength During Tableting

    OpenAIRE

    Siiriä, Simo Matti; Antikainen, Osmo; Heinämäki, Jyrki; Yliruusi, Jouko

    2011-01-01

    This study presents a new approach to model powder compression during tableting. The purpose of this study is to introduce a new discrete element simulation model for particle–particle bond formation during tablet compression. This model served as the basis for calculating tablet strength distribution during a compression cycle. Simulated results were compared with real tablets compressed from microcrystalline cellulose/theophylline pellets with various compression forces. Simulated and exper...

  7. 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…

  8. 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.

  9. 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.

  10. 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 ...

  11. COMPARISON OF SUBLINGUAL THERAPEUTIC VACCINE WITH ANTIBIOTICS FOR THE PROPHYLAXIS OF RECURRENT URINARY TRACT INFECTIONS

    OpenAIRE

    María Fernanda Lorenzo-Gómez; María Fernanda Lorenzo-Gómez; María Fernanda Lorenzo-Gómez; Bárbara ePadilla-Fernández; María Begoña García-Cenador; Álvaro Julio Virseda Rodríguez; Álvaro Julio Virseda Rodríguez; Isidoro eMartín-García; Alfonso eSánchez-Escudero; Manuel José Vicente-Arroyo; José Antonio Mirón-Canelo

    2015-01-01

    Objective: To evaluate the clinical impact of the prophylactic treatment with sublingual immunostimulation in the prevention of recurrent urinary tract infections (rUTIs) compared with the use of antibiotics.Material and Methods: Retrospective cohort study evaluating the clinical records of 669 women with rUTIs; 339 had a 6-month prophylaxis with antibiotics and 360 had a 3-month prophylaxis with a sublingual bacterial preparation (MV 140-Uromune®). The time after the prophylaxis-period until...

  12. Comparison of sublingual therapeutic vaccine with antibiotics for the prophylaxis of recurrent urinary tract infections

    OpenAIRE

    Lorenzo-G?mez, Mar?a F.; Padilla-Fern?ndez, B?rbara; Garc?a-Cenador, Mar?a B.; Virseda-Rodr?guez, ?lvaro J.; Mart?n-Garc?a, Isidoro; S?nchez-Escudero, Alfonso; Vicente-Arroyo, Manuel J.; Mir?n-Canelo, Jos? A.

    2015-01-01

    Objective: To compare the clinical impact of a prophylactic treatment with sublingual immunostimulation in the prevention of recurrent urinary tract infections (rUTIs) with the use of antibiotics. Material and Methods: Retrospective cohort study evaluating the medical records of 669 women with rUTIs; 339 had a 6-month prophylaxis with antibiotics and 360 a 3-month prophylaxis with a sublingual bacterial preparation (MV 140-Uromune®). The time frame after the prophylaxis-period until the ap...

  13. Sublingual immunotherapy for pediatric allergic rhinitis: The clinical evidence.

    Science.gov (United States)

    Poddighe, Dimitri; Licari, Amelia; Caimmi, Silvia; Marseglia, Gian Luigi

    2016-02-08

    Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient's daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure allergic respiratory diseases, by modulating the immune system activity. This review clearly summarizes and analyzes the available randomized, double-blinded, placebo-controlled trials, which aimed at evaluating the effectiveness and the safety of grass pollen and house dust mite SLIT for the specific treatment of pediatric allergic rhinitis. Our analysis demonstrates the good evidence supporting the efficacy of SLIT for allergic rhinitis to grass pollens in children, whereas trials regarding pediatric allergic rhinitis to house dust mites present lower quality, although several studies supported its usefulness.

  14. Subcutaneous and Sublingual Immunotherapy in Allergic Asthma in Children

    Directory of Open Access Journals (Sweden)

    Sophia Tsabouri

    2017-04-01

    Full Text Available This review presents up-to-date understanding of immunotherapy in the treatment of children with allergic asthma. The principal types of allergen immunotherapy (AIT are subcutaneous immunotherapy (SCIT and sublingual immunotherapy (SLIT. Both of them are indicated for patients with allergic rhinitis and/or asthma, who have evidence of clinically relevant allergen-specific IgE, and significant symptoms despite reasonable avoidance measures and/or maximal medical therapy. Studies have shown a significant decrease in asthma symptom scores and in the use of rescue medication, and a preventive effect on asthma onset. Although the safety profile of SLIT appears to be better than SCIT, the results of some studies and meta-analyses suggest that the efficacy of SCIT is better and that SCIT has an earlier onset than SLIT in children with allergic asthma. Severe, not controlled asthma, and medical error were the most frequent causes of SCIT-induced adverse events.

  15. Serum IL-9 levels and sublingual immunotherapy: preliminary report.

    Science.gov (United States)

    Ciprandi, G; De Amici, M; Marseglia, G L

    2011-01-01

    Th9 is a new T cell subset characterized by IL-9 production. It has been reported that serum IL-9 levels are related with symptom severity in patients with allergic rhinitis (AR). This study is aimed at investigating whether serum IL-9 may be modulated by sublingual immunotherapy (SLIT) in patients with persistent AR due to Parietaria allergy. Twenty-one AR patients (9 males, median age 41 years) successfully treated with SLIT and 52 AR patients (25 males, median age 34 years) treated only with drugs were evaluated during the pollen season. Serum IL-9 was dosed in all patients. SLIT-treated patients showed significantly lower serum IL-9 levels than untreated AR patients (p <0.0001). In conclusion, this preliminary study shows that a single pre-seasonal SLIT course might modulate serum IL-9.

  16. Adenoid cystic carcinoma of the sublingual gland: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ji Young [Dept. of Oral and Maxillofacial Surgery, School of Medicine, Jeju National University, Jeju (Korea, Republic of)

    2016-12-15

    Adenoid cystic carcinoma (ACC) of the sublingual gland is an extremely rare neoplasm. The clinicopathological characteristics of ACC are slow-growing swelling with or without ulceration, perineural spread, local recurrence, and distant metastasis. This report describes a 58-year-old male who had a slowly growing swelling without ulceration on the right side of the mouth floor that had been present for 1 month. In a radiological examination, the mass showed multilocular cystic features and no bony or tongue muscle invasion. No enlarged cervical lymph nodes were detected. Excisional biopsy and histological analysis showed that the lesion was ACC. In addition to reporting a rare case of ACC, this report also discusses the differential diagnosis and treatment of ACC with a review of the relevant literature.

  17. Treating allergic rhinitis by sublingual immunotherapy: a review

    Directory of Open Access Journals (Sweden)

    Cristoforo Incorvaia

    2012-06-01

    Full Text Available OBJECTIVE: Allergic rhinitis (AR is a disease with high and increasing prevalence. The management of AR includes allergen avoidance, anti-allergic drugs, and allergen specific immunotherapy (AIT, but only the latter works on the causes of allergy and, due to its mechanisms of action, modifies the natural history of the disease. Sublingual immunotherapy (SLIT was proposed in the 1990s as an option to traditional, subcutaneous immunotherapy. MATERIAL AND METHODS: We reviewed all the available controlled trials on the efficacy and safety of SLIT. RESULTS AND CONCLUSION: Thus far, more than 60 trials, globally evaluated in 6 meta-analyses, showed that SLIT is an effective and safe treatment for AR. However, it must be noted that to expect clinical efficacy in the current practice SLIT has to be performed following the indications from controlled trials, that is, sufficiently high doses to be regularly administered for at least 3 consecutive years.

  18. Histoanatomical study of the Sublingual Salivary Gland in the Camel

    Directory of Open Access Journals (Sweden)

    M.a Ebrahimi

    2008-02-01

    Full Text Available The heads of ten adult camels were used in this study. Following skin removal, the length, width and thickness of the gland was measured by ruler and caliper. Dye injection was used to distinguish the sublingual duct papilla and 1cm sections from the gland were removed and fixed to prepare histologic sections stained with H & E for microscopic studies. The long, ribbon like and lobulated monostomatic part of the gland is situated underneath the tongue alongside the hypoglossus muscle. This part of the gland begins from the mandibular symphysis and is continued caudally to near the root of the tongue. The average length, width and thickness of this part were 15.2±0.02, 2.2±0.03 and 0.5±0.05 cm respectively. The polystomatic part was observed as scattered and lobulated near the submucosa and in front of the monostomatic part with decreasing concentration caudally. The average size of these fragments was approximately 0.5±0.02 cm. The overall appearance of the gland was lobulated with a pink colour. The monostomatic part has a single duct entering the sublingual caruncle. The minute polystomatic ducts open into the depressions alongside the tongue inside the oral cavity. These ducts are numerous. Histologically, the gland is surrounded by a capsule of dense connective tissue. Trabcules from the capsule penetrate the gland and divide it into lobules. Loose connective tissue makes up the framework of the gland and there are tubulo-acinus glands in the spaces of this framework. Approximately 95% of the secretory cells of this gland consist of mucous secreting cells. Myoepithelial cells are seen on the external surface of the secretory cells and also alongside the connecting ducts.

  19. 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

  20. Baixa dose de misoprostol sublingual (12,5 µg para indução do parto Low dose of sublingual misoprostol (12.5 µg for labor induction

    Directory of Open Access Journals (Sweden)

    Daniele Sofia de Moraes Barros Gattás

    2012-04-01

    -randomized clinical trial during the period from July to December 2009. We included 30 pregnant women with an indication for labor induction at term, carrying a live fetus, with a Bishop score of six or less, cephalic presentation, estimated fetal weight of less than 4,000 g and an amniotic fluid index greater than five. We excluded women with a previous uterine scar, non-reassuring fetal status, congenital anomalies, multiple pregnancy, intrauterine growth restriction, genital bleeding, and contraindications of vaginal delivery. A tablet of 12.5 µg sublingual misoprostol was administered every six hours, until the beginning of labor, with the maximum of eight doses. RESULTS: Labor was successfully induced in 90% of pregnant women. The mean interval between the first dose and the onset of uterine contractions and delivery was 14.3±11.7 hours and 25.4±13 hours, respectively. The frequency of vaginal delivery was 60%. Uterine tachysystole occurred in two pregnant women, being reversed in both cases without the need for cesarean section. Meconium-stained amniotic fluid was observed in four patients, and an Apgar score of less than 7 at five minutes in only one newborn. CONCLUSION: Maternal and perinatal outcomes were favorable after induction of labor with sublingual misoprostol at a dose of 12.5 µg every six hours. However, controlled trials are needed to compare this regimen with other doses and routes of administration.

  1. Monitoring Microcirculatory Blood Flow with a New Sublingual Tonometer in a Porcine Model of Hemorrhagic Shock

    Directory of Open Access Journals (Sweden)

    Péter Palágyi

    2015-01-01

    Full Text Available Tissue capnometry may be suitable for the indirect evaluation of regional hypoperfusion. We tested the performance of a new sublingual capillary tonometer in experimental hemorrhage. Thirty-six anesthetized, ventilated mini pigs were divided into sham-operated (n=9 and shock groups (n=27. Hemorrhagic shock was induced by reducing mean arterial pressure (MAP to 40 mmHg for 60 min, after which fluid resuscitation started aiming to increase MAP to 75% of the baseline value (60–180 min. Sublingual carbon-dioxide partial pressure was measured by tonometry, using a specially coiled silicone rubber tube. Mucosal red blood cell velocity (RBCV and capillary perfusion rate (CPR were assessed by orthogonal polarization spectral (OPS imaging. In the 60 min shock phase a significant drop in cardiac index was accompanied by reduction in sublingual RBCV and CPR and significant increase in the sublingual mucosal-to-arterial PCO2 gap (PSLCO2 gap, which significantly improved during the 120 min resuscitation phase. There was significant correlation between PSLCO2 gap and sublingual RBCV (r=-0.65, p<0.0001, CPR (r=-0.64, p<0.0001, central venous oxygen saturation (r=-0.50, p<0.0001, and central venous-to-arterial PCO2 difference (r=0.62, p<0.0001. This new sublingual tonometer may be an appropriate tool for the indirect evaluation of circulatory changes in shock.

  2. Tabletability Modulation Through Surface Engineering.

    Science.gov (United States)

    Osei-Yeboah, Frederick; Sun, Changquan Calvin

    2015-08-01

    Poor powder tabletability is a common problem that challenges the successful development of high-quality tablet products. Using noncompressible microcrystalline cellulose beads, we demonstrate that surface coating is an effective strategy for modulating tabletability, almost at will, through judicious selection of coating material. This strategy has broad applicability as tabletability of such particles is dictated by the properties of the outermost layer coat regardless the nature of the core. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  3. 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.

  4. 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...

  5. 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.

  6. 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).

  7. 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

  8. 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....

  9. [Tablets and tablet production - with special reference to Icelandic conditions].

    Science.gov (United States)

    Skaftason, Jóhannes F; Jóhannesson, Thorkell

    2013-04-01

    Modern tablet compression was instituted in England in 1844 by William Brockedon (1787-1854). The first tablets made according to Brockedon´s procedures contained watersoluble salts and were most likely compressed without expedients. In USA a watershed occurred around 1887 when starch (amylum maydis) was introduced to disperse tablets in aqueous milieu in order to corroborate bioavailability of drugs in the almentary canal. About the same time great advances in tablet production were introduced by the British firm Burroughs Wellcome and Co. In Denmark on the other hand tablet production remained on low scale until after 1920. As Icelandic pharmacies and drug firms modelled themselves mostly upon Danish firms tablet production was first instituted in Iceland around 1930. The first tablet machines in Iceland were hand-driven. More efficent machines came after 1945. Around 1960 three sizeable tablet producers were in Iceland; now there is only one. Numbers of individual tablet species (generic and proprietary) on the market rose from less than 10 in 1913 to 500 in 1965, with wide variations in numbers in between. Tablets have not wiped out other medicinal forms for peroral use but most new peroral drugs have been marketed in the form of tablets during the last decades.

  10. 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

  11. 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.

  12. 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.

  13. 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...

  14. 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...

  15. 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

  16. Fentanyl transmucosal tablets: current status in the management of cancer-related breakthrough pain

    Directory of Open Access Journals (Sweden)

    Prommer E

    2012-06-01

    Full Text Available Eric Prommer, Brandy FicekDivision of Hematology/Oncology, Mayo Clinic College of Medicine, Mayo Clinic Hospital, Scottsdale, AZ, USAAbstract: Breakthrough pain is a newly recognized pain category that was first described by Portenoy and Hagen in 1990. The term describes pain that increases in intensity to “break through” chronic pain that is being controlled by a scheduled opioid regimen. The development of fluctuations in pain intensity is challenging due to their unpredictable nature, rapid onset, and need for rapid treatment intervention. Breakthrough pain has been treated by using an extra opioid dose in addition to the scheduled opioid being used for pain. Recommendations for dose and frequency are based on expert opinion only, and have included dosing based on a percentage of the total opioid dose. Other recommendations include increasing the regularly scheduled opioid dose. Clinical trials have now focused on delivery of opioids that have both potency and a rapid onset of action. Lipophilic opioids have received a substantial amount of study due to their quick absorption and rapid onset of analgesia. Lipophilic opioids that have been studied to date include transmucosal fentanyl, sublingual fentanyl, intranasal sufentanil, and oral and sublingual methadone. Initial clinical trials have established the superiority of transmucosal fentanyl as a breakthrough analgesic when compared with immediate-release oral opioid formulations. Problems with bioavailability have led to a search for newer formulations of transmucosal delivery. Newer formulations, such as fentanyl transmucosal tablets, have been developed to ensure superior delivery for the patient suffering from breakthrough pain. The purpose of this paper is to discuss the current status of transmucosal tablet formulations for cancer breakthrough pain.Keywords: fentanyl, transmucosal, tablets, pain, breakthrough, cancer

  17. Teach yourself visually Fire tablets

    CERN Document Server

    Marmel, Elaine

    2014-01-01

    Expert visual guidance to getting the most out of your Fire tablet Teach Yourself VISUALLY Fire Tablets is the comprehensive guide to getting the most out of your new Fire tablet. Learn to find and read new bestsellers through the Kindle app, browse the app store to find top games, surf the web, send e-mail, shop online, and much more! With expert guidance laid out in a highly visual style, this book is perfect for those new to the Fire tablet, providing all the information you need to get the most out of your device. Abundant screenshots of the Fire tablet graphically rich, touch-based Androi

  18. The Nebusarsekim Tablet

    NARCIS (Netherlands)

    Stadhouders, H.A.I.

    2008-01-01

    During the summer of 2007 an internet hype was unleashed by the breaking news that an Old Testament name of some importance, figuring in the Book of Jeremiah Ch. 39, had been positively identified on a cuneiform clay tablet, viz. a bill of receipt from the time of this prophet's floruit. Many a

  19. 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

  20. The effect of an electronic medicine dispenser on diversion of buprenorphine-naloxone-experience from a medium-sized Finnish city.

    Science.gov (United States)

    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.

  1. 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

  2. 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.

  3. Morphology and morphometry of the human sublingual glands in mouth floor enlargements of edentulous patients

    Directory of Open Access Journals (Sweden)

    Josiane Costa Rodrigues de SA

    2013-12-01

    Full Text Available Asymptomatic mouth floor enlargements may be observed in edentulous patients. These masses, which protrude from the mouth floor, may complicate the fitting of dentures and require surgery. Whether this "entity" may be considered an anatomical variation of the mouth floor or represent specific alterations in the sublingual gland is not known. Objective: The aim of this work is to investigate the morphological and morphometric aspects of the sublingual glands of edentulous patients with mouth floor enlargements and compare the glands of these patients with the sublingual glands of human cadavers. Material and Methods: Microscopic evaluation was performed on human sublingual glands from edentulous patients with mouth floor enlargements (n=20 and edentulous cadavers (n=20. The patients and cadavers were of similar ages. The data were compared using Mann-Whitney U, Fisher's exact and Student's t tests (p0.05. Only the variables "autolysis" and "congested blood vessels" presented statistical difference between groups (p=0.014; p=0.043. The morphometric study revealed that the volume densities of acini, ducts, stroma and adipose tissue were similar between the groups (p>0.05. CONCLUSION: The microscopic characteristics of the sublingual glands in mouth floor enlargements in edentulous patients correspond to characteristics associated with the normal aging process. The glands are not pathological and represent an age-related alteration that occurs with or without the presence of the mouth floor enlargements.

  4. Sublingual Nitroglycerin Administration in Coronary Computed Tomography Angiography: a Systematic Review.

    Science.gov (United States)

    Takx, Richard A P; Suchá, Dominika; Park, Jakob; Leiner, Tim; Hoffmann, Udo

    2015-12-01

    To systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography. A systematic search was performed in PubMed, EMBASE and Web of Science. The studies were evaluated for the effect of sublingual nitroglycerin on coronary artery diameter, evaluable segments, objective and subjective image quality, systemic physiological effects and diagnostic accuracy. Due to the heterogeneous reporting of outcome measures, a narrative synthesis was applied. Of the 217 studies identified, nine met the inclusion criteria: seven reported on the effect of nitroglycerin on coronary artery diameter, six on evaluable segments, four on image quality, five on systemic physiological effects and two on diagnostic accuracy. Sublingual nitroglycerin administration resulted in an improved evaluation of more coronary segments, in particular, in smaller coronary branches, better image quality and improved diagnostic accuracy. Side effects were mild and were alleviated without medical intervention. Sublingual nitroglycerin improves the coronary diameter, the number of assessable segments, image quality and diagnostic accuracy of coronary CT angiography without major side effects or systemic physiological changes. • Sublingual nitroglycerin administration results in significant coronary artery dilatation. • Nitroglycerin increases the number of evaluable coronary branches. • Image quality is improved the most in smaller coronary branches. • Nitroglycerin increases the diagnostic accuracy of coronary CT angiography. • Most side effects are mild and do not require medical intervention.

  5. Sublingual desmopressin is efficient and safe in the therapy of lithiasic renal colic.

    Science.gov (United States)

    Pricop, Catalin; Branisteanu, Dumitru D; Orsolya, Martha; Puia, Dragos; Matei, Anca; Checherita, Ionel Alexandru

    2016-02-01

    To evaluate the effects of newer sublingual desmopressin administration in lithiasic renal colic, alone or combined with a nonsteroidal anti-inflammatory drug (NSAID). Prospective single-blind study including an initial number of 249 patients with lithiasic renal colic was randomized as follows: group NSAID (71 patients) received ketorolac tromethamine (ketorolac) 30 mg im and sublingual placebo (vitamin C), groups D1 and D2 (57 and 62 patients) received sublingual desmopressin (Minirin Melt), 60 and 120 μg, respectively, whereas group C (59 patients) received a combination of 30 mg im ketorolac and 60 μg sublingual desmopressin. Pain intensity was assessed using the visual analogue scale before and thirty minutes after drug administration. Patients experiencing pain aggravation were rescued and excluded from the study. Dropout incidence was higher in the NSAID group than in the groups treated with desmopressin in monotherapy or combined with ketorolac (p desmopressin and ketorolac. The higher dose of desmopressin and the combination therapy decreased pain intensity with 56 and 59%, respectively, significantly more than the 47% decrease obtained with ketorolac alone (p desmopressin is at least as potent as NSAID in the treatment of lithiasic renal colic. The combination of sublingual desmopressin and NSAID has additive analgesic effects.

  6. Salivary lactoferrin is transferred into the brain via the sublingual route.

    Science.gov (United States)

    Hayashi, Takashi; To, Masahiro; Saruta, Juri; Sato, Chikatoshi; Yamamoto, Yuko; Kondo, Yusuke; Shimizu, Tomoko; Kamata, Yohei; Tsukinoki, Keiichi

    2017-07-01

    Lactoferrin (LF) is produced by exocrine glands including salivary gland, and has various functions including infection defense. However, the transfer of LF from peripheral organs into the brain remains unclear. To clarify the kinetics of salivary LF (sLF), we investigated the consequences of sialoadenectomy and bovine LF (bLF) sublingual administration in rats. The salivary glands were removed from male Wistar rats, and we measured rat LF levels in the blood and brain at 1 week post-surgery. We also examined the transfer of LF into the organs of the rats after sublingual administration of bLF. Rat LF levels in the blood and brain were significantly reduced by sialoadenectomy. Sublingual bLF administration significantly increased bLF levels in the brain, which then decreased over time. These results indicate that LF is transferred from the sublingual mucosa to the brain, in which favorable effects of sLF on brain will be expected via the sublingual mucosa.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Olaparib tablet formulation

    DEFF Research Database (Denmark)

    Plummer, Ruth; Swaisland, Helen; Leunen, Karin

    2015-01-01

    formulation. METHODS: PK data were obtained in Part A using a two-treatment period crossover design; single-dose olaparib 300 mg (two 150 mg tablets) was administered in two prandial states: fasted and fed. In Part B, patients received olaparib tablets (300 mg bid) for 5 days under fasting conditions; in Part...... C, patients were allowed continued access to olaparib. Safety was assessed throughout, with data reported for Parts A and B. RESULTS: A total of 60 and 56 patients were evaluable for safety and PK analyses, respectively; 57 patients entered Part B. Rate of olaparib absorption was slower.......16)]. The point estimate and 90 % CI for the AUC0-∞ treatment ratio were within pre-defined bioequivalence limits (0.80-1.25). Adverse event data were consistent with the known safety profile of olaparib. CONCLUSIONS: Results of this study showed that a high-fat meal decreases the rate of absorption and peak...

  14. 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

    Directory of Open Access Journals (Sweden)

    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.

  15. Selection of patients for sublingual versus subcutaneous immunotherapy.

    Science.gov (United States)

    Larenas Linnemann, Désirée E S; Blaiss, Michael S

    2014-01-01

    Allergen immunotherapy is the sole treatment for IgE-mediated allergic diseases directed at the underlying mechanism. The two widely accepted administration routes are sublingual (SLIT) and subcutaneous (SCIT). We reviewed how patients should best be selected for immunotherapy and how the optimal administration route can be defined. Before deciding SCIT or SLIT, appropriate selection of patients for allergen immunotherapy (AIT) is mandatory. To be eligible for AIT, subjects must have a clear medical history of allergic disease, with exacerbation of symptoms on exposure to one or more allergens and a corresponding positive skin or in vitro test. Then the route of administration should be based on: published evidence of clinical and immunologic efficacy (which varies per allergic disease and per allergen); mono- or multi-allergen immunotherapy, for SLIT multi-allergen immunotherapy was not effective; safety: adverse events with SLIT are more frequent, but less severe; and, costs and patient preferences, closely related to adherence issues. All these are discussed in the article.

  16. Local Side Effects of Sublingual and Oral Immunotherapy.

    Science.gov (United States)

    Passalacqua, Giovanni; Nowak-Węgrzyn, Anna; Canonica, Giorgio Walter

    Sublingual immunotherapy (SLIT) is increasingly used worldwide, and several products have been recently registered as drugs for respiratory allergy by the European Medicine Agency and the Food and Drug Administration. Concerning inhalant allergens, the safety of SLIT is overall superior to that of subcutaneous immunotherapy in terms of systemic adverse events. No fatality has been ever reported, and episodes of anaphylaxis were described only exceptionally. Looking at the historical and recent trials, most (>90%) adverse events are "local" and confined to the site of administration. For this reason, a specific grading system has been developed by the World Allergy Organization to classify and describe local adverse events. There is an increasing amount of literature concerning oral desensitization for food allergens, referred to as oral immunotherapy. Also, in this case, local side effects are predominant, although systemic adverse events are more frequent than with inhalant allergens. We review herein the description of local side effects due to SLIT, with a special focus on large trials having a declared sample size calculation. The use of the Medical Dictionary for Regulatory Activities nomenclature for adverse events is mentioned in this context, as recommended by regulatory agencies. It is expected that a uniform classification/grading of local adverse events will improve and harmonize the surveillance and reporting on the safety of SLIT. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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...

  7. 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.

  8. 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.

  9. Sharp tooth induced sublingual hematoma in a patient with elevated international normalized ratio

    Directory of Open Access Journals (Sweden)

    John Baliah

    2015-01-01

    Full Text Available Sublingual hematoma secondary to anticoagulation is a rare fatal condition. Hemorrhagic complications of warfarin are well-known. This particular case is unique because the patient was on warfarin for the past 2 years but did not develop the sublingual hematoma. However, a trauma by an attrited sharp cusp triggered the episode of the sublingual hematoma in this patient. Being a medical emergency, patient was promptly hospitalized in cardiac care unit and managed by medical team. The patient was transfused with 2 units of fresh frozen plasma and warfarin was temporarily stopped for 4 days. Alternate day regimen of warfarin was started after 4 days, and international normalized ratio dropped to 3. In dental management, enameloplasty of the mandibular first molar tooth was done to prevent trauma and ulcer development in the floor of the mouth. The hematoma resolved, and no new hematoma formation was observed for a period of 6 months.

  10. 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.

  11. 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

  12. 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.

  13. Sublingual immunotherapy in polysensitized patients: effect on quality of life.

    Science.gov (United States)

    Ciprandi, G; Cadario, G; Valle, C; Ridolo, E; Verini, M; Di Gioacchino, M; Minelli, M; Gangemi, S; Sillano, V; Colangelo, C; Pravettoni, V; Pellegrino, R; Borrelli, P; Fiorina, A; Carosso, A; Gasparini, A; Riario-Sforza, G G; Incorvaia, C; Puccinelli, P; Scurati, S; Frati, F

    2010-01-01

    Quality of life (QOL) is an important issue in allergic rhinitis and has been evaluated in a number of studies that have shown how it is impaired in untreated patients and improved by effective treatment. However, there are no data concerning QOL after sublingual immunotherapy (SLIT) in polysensitized patients. To evaluate the effect, in real-life clinical practice, of SLIT on QOL in a population of polysensitized patients with allergic rhinitis. We prospectively evaluated 167 consecutively enrolled polysensitized patients with allergic rhinitis. QOL was measured in all cases with the Rhinoconjunctivitis Quality of Life Questionnaire at baseline and after 1 year of SLIT (performed in approximately 70% of cases using single allergen extracts provided by the same manufacturer). The most frequent causes of sensitization were grass pollen, Parietaria, and house dust mites. The mean number of sensitizations per patient was 3.65. SLIT was performed with 1 extract in 123 patients (73.6%), with 2 extracts in 31 patients (18.6%), and with more than 2 extracts in 13 patients (7.8%). The mean values of all the QOL items improved significantly (P < .01 in all cases), with the following reductions noted: activities, 3.96 to 2.89; sleep, 2.07 to 1.56; general problems, 2.16 to 1.5; practical problems, 3.69 to 2.58; nasal symptoms, 3.57 to 2.50; eye symptoms, 2.92 to 1.83; and emotional aspects, 2.2 to 1.44. This study provides evidence that QOL can be improved in polysensitized patients treated with SLIT, and that the use of just 1 or 2 allergen extracts seems to be sufficient and effective in terms of improving QOL.

  14. Tablets i skolen

    DEFF Research Database (Denmark)

    Lorentzen, Rasmus Fink

    2012-01-01

    Denne rapport afslutter CELMS undersøgelse af Odder Kommunes projekt med indførelse af iPads på alle kommunens skoler. Undersøgelsen har til formål at belyse om der er pædagogiske og læringsmæssige fordele forbundet med brugen af tablets i undervisningen i grundskolen og i givet fald hvilke...... designer og tablet’ens egenskaber i et generelt perspektiv. Rapporten afsluttes med en række anbefalinger til henholdsvis lærere og skoleledere med henblik på videre udvikling af indsatsen....

  15. Review of bilayer tablet technology.

    Science.gov (United States)

    Abebe, Admassu; Akseli, Ilgaz; Sprockel, Omar; Kottala, Niranjan; Cuitiño, Alberto M

    2014-01-30

    Therapeutic strategies based on oral delivery of bilayer (and multilayer) tablets are gaining more acceptance among brand and generic products due to a confluence of factors including advanced delivery strategies, patient compliance and combination therapy. Successful manufacturing of these ever more complex systems needs to overcome a series of challenges from formulation design to tablet press monitoring and control. This article provides an overview of the state-of-the-art of bilayer tablet technology, highlighting the main benefits of this type of oral dosage forms while providing a description of current challenges and advances toward improving manufacturing practices and product quality. Several aspects relevant to bilayer tablet manufacturing are addressed including material properties, lubrication, layer ordering, layer thickness, layer weight control, as well as first and final compression forces. A section is also devoted to bilayer tablet characterization that present additional complexities associated with interfaces between layers. The available features of the manufacturing equipment for bilayer tablet production are also described indicating the different strategies for sensing and controls offered by bilayer tablet press manufacturers. Finally, a roadmap for bilayer tablet manufacturing is advanced as a guideline to formulation design and selection of process parameters and equipment. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Windows for tablets for dummies

    CERN Document Server

    Rathbone, Andy

    2013-01-01

    Just for you--Windows 8 from the tablet user's perspective If you're an experienced Windows user, you don't need a guide to everything that Windows 8 can do, just to those tools and functions that work on your tablet. And so here it is. This new book zeros in on what you need to know to work best on your tablet with Windows 8. Topics include navigating the new Windows 8 interface and how it works on a touchscreen, how to safely connect to the Internet, how to work with apps or share your tablet in a group, and much more. If you're a new tablet user, you'll particularly appre

  17. 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

  18. 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.

  19. 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.

  20. Efficacy and Safety of Transdermal Buprenorphine versus Oral Tramadol/Acetaminophen in Patients with Persistent Postoperative Pain after Spinal Surgery

    Directory of Open Access Journals (Sweden)

    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.

  1. 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.

  2. 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.

  3. 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...

  4. Sublingual immunotherapy not effective in house dust mite-allergic children in primary care

    NARCIS (Netherlands)

    de Bot, Cindy M. A.; Moed, Heleen; Berger, Marjolein Y.; Roder, Esther; Hop, Wim C. J.; de Groot, Hans; de Jongste, Johan C.; van Wijk, Roy Gerth; Bindels, Patrick J. E.; van der Wouden, Johannes C.

    Background: Sublingual immunotherapy (SLIT) as a therapy for the treatment of allergic rhinitis in children might be acceptable as an alternative for subcutaneous immunotherapy. However, the efficacy of SLIT with house dust mite extract is not well established. Objective: To investigate whether SLIT

  5. Sublingual immunotherapy with grass pollen is not effective in symptomatic youngsters in primary care

    NARCIS (Netherlands)

    Roder, Esther; Berger, Marjolein Y.; Hop, Wim C. J.; Bernsen, Roos M. D.; de Groot, Hans; van Wijk, Roy Gerth

    Background: Sublingual immunotherapy (SLIT) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care. Most efficacy studies in children lack power to be conclusive, and all have been performed in

  6. Sublingual immunotherapy in children with allergic rhinitis : quality of systematic reviews

    NARCIS (Netherlands)

    de Bot, Cindy M. A.; Moed, Heleen; Berger, Marjolein Y.; Roeder, Esther; van Wijk, Roy G.; van der Wouden, Johannes C.

    Systematic reviews have gained popularity as a way to combine the increasing amount of research information. This study assessed the quality of systematic reviews and meta-analyses of sublingual immunotherapy (SLIT) for allergic rhinitis in children, published since 2000. Eligible reviews were

  7. Neutrophils negatively regulate induction of mucosal IgA responses after sublingual immunization.

    Science.gov (United States)

    Jee, J; Bonnegarde-Bernard, A; Duverger, A; Iwakura, Y; Cormet-Boyaka, E; Martin, T L; Steiner, H E; Bachman, R C; Boyaka, P N

    2015-07-01

    Induction of mucosal immunoglobulin-A (IgA) capable of providing a first line of defense against bacterial and viral pathogens remains a major goal of needle-free vaccines given via mucosal routes. Innate immune cells are known to play a central role in induction of IgA responses by mucosal vaccines, but the relative contribution of myeloid cell subsets to these responses has not firmly been established. Using an in vivo model of sublingual vaccination with Bacillus anthracis edema toxin (EdTx) as adjuvant, we examined the role of myeloid cell subsets for mucosal secretory IgA responses. Sublingual immunization of wild-type mice resulted in a transient increase of neutrophils in sublingual tissues and cervical lymph nodes. These mice later developed Ag-specific serum IgG responses, but not serum or mucosal IgA. Interestingly, EdTx failed to increase neutrophils in sublingual tissues and cervical lymph nodes of IKKβ(ΔMye) mice, and these mice developed IgA responses. Partial depletion of neutrophils before immunization of wild-type mice allowed the development of both mucosal and serum IgA responses. Finally, co-culture of B cells with neutrophils from either wild-type or IKKβ(ΔMye) mice suppressed secretion of IgA, but not IgM or IgG. These results identify a new role for neutrophils as negative regulators of IgA responses.

  8. Comparison of Drug Acceptance and Anxiety Between Intranasal and Sublingual Midazolam Sedation.

    Science.gov (United States)

    Shanmugaavel, A Karthikeyan; Asokan, Sharath; John, J Baby; Priya, P R Geetha; Raaja, M Thirumalai

    2016-01-01

    The purpose of the study was to assess and compare the changes in anxiety level and drug acceptance after intranasal and sublingual midazolam sedation. Forty three- to seven-year-olds were randomly assigned to Group A (N equals 20; 0.2 mg/kg intranasal midazolam sedation) or Group B (N equals 20; 0.2 mg/kg sublingual midazolam sedation) sedation. The anxiety levels at various time periods were assessed from recorded videos using the Venham clinical anxiety scale by two pediatric dentists. The acceptance of the drug administration was assessed using a four-point scale. The Wilcoxon signed rank test and Mann-Whitney U test were used for statistical analysis using SPSS 17.0 software. There was a significant decrease in anxiety level from baseline to 20 minutes after drug administration in Group A (Pintranasal route of drug administration. Both intranasal and sublingual administrations of midazolam were equally effective in reducing the child's anxiety. The sublingual route of drug administration was better accepted than the intranasal route.

  9. Sublingual nitroglycerin used in routine tilt testing provokes a cardiac output-mediated vasovagal response

    NARCIS (Netherlands)

    Gisolf, J.; Westerhof, B.E.; Dijk, N. van; Wesseling, K.H.; Wieling, W.; Karemaker, J.M.

    2004-01-01

    Objectives We set out to determine the effect of sublingual nitroglycerin (NTG), as used during routine tilt testing in patients with unexplained syncope, on hemodynamic characteristics and baroreflex control of heart rate (HR) and systemic vascular resistance (SVR). Background Nitroglycerin is used

  10. Sublingual nitroglycerin administration in coronary computed tomography angiography: a systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Takx, Richard A.P. [Harvard Medical School, Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Boston, MA (United States); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Sucha, Dominika; Leiner, Tim [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Park, Jakob [Harvard Medical School, Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Boston, MA (United States); University of Heidelberg, Department of Cardiology, Heidelberg (Germany); Hoffmann, Udo [Harvard Medical School, Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Boston, MA (United States)

    2015-12-15

    To systematically investigate the literature for the influence of sublingual nitroglycerin administration on coronary diameter, the number of evaluable segments, image quality, heart rate and blood pressure, and diagnostic accuracy of coronary computed tomography (CT) angiography. A systematic search was performed in PubMed, EMBASE and Web of Science. The studies were evaluated for the effect of sublingual nitroglycerin on coronary artery diameter, evaluable segments, objective and subjective image quality, systemic physiological effects and diagnostic accuracy. Due to the heterogeneous reporting of outcome measures, a narrative synthesis was applied. Of the 217 studies identified, nine met the inclusion criteria: seven reported on the effect of nitroglycerin on coronary artery diameter, six on evaluable segments, four on image quality, five on systemic physiological effects and two on diagnostic accuracy. Sublingual nitroglycerin administration resulted in an improved evaluation of more coronary segments, in particular, in smaller coronary branches, better image quality and improved diagnostic accuracy. Side effects were mild and were alleviated without medical intervention. Sublingual nitroglycerin improves the coronary diameter, the number of assessable segments, image quality and diagnostic accuracy of coronary CT angiography without major side effects or systemic physiological changes. (orig.)

  11. Changes in sublingual microcirculatory flow index and vessel density on ascent to altitude

    NARCIS (Netherlands)

    Martin, Daniel S.; Goedhart, Peter; Vercueil, Andre; Ince, Can; Levett, Denny Z. H.; Grocott, Mike P. W.

    2010-01-01

    We hypothesized that ascent to altitude would result in reduced sublingual microcirculatory flow index (MFI) and increased vessel density. Twenty-four subjects were studied using sidestream dark-field imaging, as they ascended to 5300 m; one cohort remained at this altitude (n = 10), while another

  12. effect of pre-operative sub-lingual misoprostol versus intravenous ...

    African Journals Online (AJOL)

    2012-09-09

    Sep 9, 2012 ... infusion of oxytocin in reducing blood loss at Caesarean section operation. However, .... is the type 2 error, σ is the standard deviation, and d .... Table 3. Comparison of means of intravenous oxytocin versus sub-lingual misoprostol. Variable. Diff of mean. Std Error. Signif. 95%. CI. IV. Oxytoc. Sub-ling.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. Premedication with benzodiazepines for upper gastrointestinal endoscopy: Comparison between oral midazolam and sublingual alprazolam

    Directory of Open Access Journals (Sweden)

    Vahid Sebghatollahi

    2017-01-01

    Full Text Available Background: Premedication with orally administered benzodiazepines is effective in reducing anxiety and discomfort related to endoscopic procedures. We evaluated the efficacy and safety of oral midazolam in comparison to sublingual alprazolam as premedication for esophagogastroduodenoscopy (EGD. Materials and Methods: Adult candidates for diagnostic EGD received either oral midazolam (7.5 mg in 15 cc apple juice or sublingual alprazolam (0.5 mg 30 min before EGD. Procedural anxiety and pain/discomfort were assessed using 11-point numerical rating scales. Patients' overall tolerance (using a four-point Likert scale and willingness to repeat the EGD, if necessary, were also assessed. Blood pressure, heart rate, and arterial oxygen saturation were monitored from medication to 30 min after the procedure. Results: Patients experienced a similar reduction in procedural anxiety after medication with oral midazolam and sublingual alprazolam; mean (standard deviation [SD] of 1.86 [1.63] and 2.02 [1.99] points, respectively, P = 0.91. Compared to oral midazolam, pain/discomfort scores were lower with sublingual alprazolam; mean (SD of 4.80 (3.01 versus 3.68 (3.28, P = 0.024. There was no significant difference between the two groups in patients' tolerance, willingness to repeat the procedure, or hemodynamic events. Conclusion: Oral midazolam and sublingual alprazolam are equally effective in reducing EGD-related anxiety; however, EGD-related pain/discomfort is lower with alprazolam. Both benzodiazepines are equally safe and can be used as premedication for patients undergoing diagnostic EGD.

  20. 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.

  1. Sublingual flagellin protects against acute pneumococcal pneumonia in a TLR5-dependent and NLRC4-independent fashion.

    Science.gov (United States)

    Muñoz-Wolf, Natalia; Rial, Analía; Fougeron, Delphine; Tabareau, Julien; Sirard, Jean-Claude; Chabalgoity, José A

    2016-09-01

    To evaluate efficacy of sublingual flagellin to treat acute pneumonia. Mice were treated sublingually with flagellin and challenged intranasally with a lethal dose of pneumococcus. Flagellins lacking TLR5 or NLRC4 activation domains were used to assess their contribution to protection. Sublingual flagellin protected mice in a TLR5-dependent, NLRC4-independent fashion. Neutrophils were required for protection. Flagellin-stimulated lung epithelial cells recapitulated the lung's transcriptional profile suggesting they could be targeted by flagellin in vivo. Ligation of TLR5, a pathogen recognition receptor not naturally engaged by pneumococcus, protects mice from invasive pneumonia when administered via sublingual route. This can be a highly cost-effective alternative therapy against pneumonia.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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....

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Warfarin-induced sublingual hematoma mimicking Ludwig angina: Conservative management of a potentially life-threatening condition.

    LENUS (Irish Health Repository)

    Cashman, Emma

    2011-02-01

    Sublingual hematoma secondary to excessive anticoagulation is a rare, life-threatening condition. Reports in the literature have emphasized the importance of a prompt reversal of the causative coagulopathy by intravenous administration of vitamin K and fresh frozen plasma. In the event of an unstable airway, surgical intervention via tracheostomy or cricothyroidectomy is advocated. We report a case of sublingual hematoma that was treated conservatively, and we discuss the presentation and management of this entity.

  13. Warfarin-induced sublingual hematoma mimicking Ludwig angina: Conservative management of a potentially life-threatening condition.

    LENUS (Irish Health Repository)

    Cashman, Emma

    2012-02-01

    Sublingual hematoma secondary to excessive anticoagulation is a rare, life-threatening condition. Reports in the literature have emphasized the importance of a prompt reversal of the causative coagulopathy by intravenous administration of vitamin K and fresh frozen plasma. In the event of an unstable airway, surgical intervention via tracheostomy or cricothyroidectomy is advocated. We report a case of sublingual hematoma that was treated conservatively, and we discuss the presentation and management of this entity.

  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. 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.

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. 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

  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. Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements.

    Science.gov (United States)

    Donaldson, M S

    2000-01-01

    Pure vegetarian diets might cause cobalamin deficiency due to lack of dietary intake. It was hypothesized that a population following a vegan diet consuming mostly raw fruits and vegetables, carrot juice, and dehydrated barley grass juice would be able to avoid vitamin B12 deficiency naturally. Subjects were recruited at a health ministers' reunion based on adherence to the Hallelujah diet for at least 2 years. Serum cobalamin and urinary methylmalonic acid (MMA) assays were performed. Follow-up with sublingual tablets, nutritional yeast, or probiotic supplements was carried out on subjects with abnormal MMA results. 49 subjects were tested. Most subjects (10th to 90th percentile) had followed this diet 23-49 months. 6 subjects had serum B12 concentrations nutritional yeast, but not probiotic supplements, significantly reduced group mean MMA concentrations (tablet p 0.20). The urinary MMA assay is effective for identifying early metabolic cobalamin deficiency. People following the Hallelujah diet and other raw-food vegetarian diets should regularly monitor their urinary MMA levels, consume a sublingual cobalamin supplement, or consume cobalamin in their food.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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).

  13. 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.

  14. 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.

  15. 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

  16. Adverse reactions and tolerability of high-dose sublingual allergen immunotherapy

    Directory of Open Access Journals (Sweden)

    Moral A

    2016-06-01

    Full Text Available Angel Moral,1 Victoria Moreno,2 Francisco Girón,3 David El-Qutob,4 José D Moure,5 Manuel Alcántara,6 Antonia Padial,7 Alberto G Oehling,8 Carmen Millán,9 Fernando de la Torre10 1Allergy Service, Hospital Virgen del Valle, Toledo, 2Allergy Service, Hospital Blanca Paloma, Huelva, 3Consulta Privada, Granada, 4Allergy Service, Clínica Atenea, Castellón, 5Pediatric Department, Complejo Hospitalario Universitario de Santiago, A Coruña, 6Allergy Service, Complejo Hospitalario de Jaén, Jaén, 7Allergy Service, Hospital Infanta Sofía, Madrid, 8Centro de Alergia y Asma Balear, Mallorca, 9Consulta Privada, Cádiz, 10ALK-Abelló, SA, Madrid, Spain Background: Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy.Patients and methods: A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months.Results: The most frequent adverse reaction was oral pruritus (13.7% of the patients. Most of the reactions were local (84.7% and immediate (93.5% and occurred during the initiation phase (60.6%. All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417, age (P=0.1801, years since the disease was first

  17. 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.

  18. 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...

  19. 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.

  20. Budget impact analysis of the fentanyl buccal tablet for treatment of breakthrough cancer pain

    Directory of Open Access Journals (Sweden)

    Darbà J

    2013-12-01

    Full Text Available Josep Darbà,1 Lisette Kaskens,2 Rainel Sánchez-de la Rosa31University of Barcelona, Barcelona, 2BCN Health Economics and Outcomes Research SL, Barcelona, 3Medical and HEOR Department, TEVA Pharmaceutical Industries Ltd, Madrid, SpainBackground: The purpose of this study was to assess the economic impact of the fentanyl buccal tablet for the management of breakthrough cancer pain (BTcP in Spain.Methods: A 4-year budget impact model was developed for the period 2012–2015 for patients with BTcP from the perspective of the Spanish National Health System. BTcP products included in this model were rapid-onset opioids containing fentanyl (buccal, sublingual, or nasal transmucosal. Prevalence data on cancer, BTcP, opioid use, and number of BTcP episodes were obtained from the literature. Input data on health care resources associated with opioid use and opioid-induced side effects were obtained by consulting experts in oncology from different Spanish hospitals. Resources used included drugs, medical and emergency visits, other nonpharmacologic treatments, and treatment of opioid-induced side effects. Unit costs were obtained from the literature, and a 3% discount rate was applied to costs. Based on the unit costs for drugs and health care resources, the annual BTcP treatment costs per patient associated with each fentanyl product were determined to estimate the overall budget impact based on the total treatment population and the percentage of drug utilization associated with each product. One-way sensitivity analyses were conducted to test the robustness of the model.Results: Patients treated with oral opioids for BTcP were estimated at 23,291 in 2012, with an increase up to 23,413 in 2015. The average annual budget savings, with an increase of fentanyl buccal tablets, fentanyl sublingual tablets, and intranasal fentanyl spray, and a decrease in oral transmucosal fentanyl citrate, was estimated at €2.6 million, which represents a 0.5% decrease in

  1. Assessing tablet bond types from structural features that affect tablet tensile strength.

    Science.gov (United States)

    Olsson, H; Nyström, C

    2001-02-01

    The aim of this article was to study the possibility of assessing the structural features affecting tablet tensile strength to obtain information on the dominating bond types, i.e. interparticulate attractions, in tablets. The features of the internal tablet structure considered to be important for tablet tensile strength were assessed using a simple tablet model for tablets made from seven materials: potassium chloride, sodium chloride, sodium bicarbonate, lactose, sucrose, microcrystalline cellulose, and ascorbic acid. Tablet porosity and particle size (measured as external specific surface area by permeametry) were the structural features that best correlated with tablet tensile strength. These features were described by a "structural factor," which was combined with tablet tensile strength, as an "interaction factor," to reflect the dominating bond types in tablets. The qualitative results gave dominating bond types in the tablets studied that matched the results of earlier studies, thus supporting the applicability of the method.

  2. [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.

  3. Reduced sublingual endothelial glycocalyx in type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Winther, Signe Abitz; Frimodt-Møller, Marie; Zobel, Emilie Hein

    - and macroalbuminuric patients (p=0.020) and micro- and macroalbuminuric patients (p=0.042) were significant, but the difference between normo- and microalbuminuric patients was not (p=0.74). After adjustment for age, sex, HbA1c, diabetes duration and systolic blood pressure, differences between normo...... of easy and non-invasive quantification tools. With capillaroscopy it is possible to visualize the sublingual capillaries by sidestream dark field imaging and estimates the dimensions of the glycocalyx by measuring the perfused boundary region (PBR). We evaluated the glycocalyx thickness non-invasively...... thickness was assessed by 5 measurements with the GlucoCheck device (GlucoCheck BV, The Netherlands), a non-invasive hand-held microscope generating video recordings of the sublingual capillaries. Endothelial glycocalyx thickness was estimated from the PBR in capillaries with a diameter range of 5-25 μm...

  4. CHANGES OF IMMUNE INDEXES DURING SUBLINGUAL ALLERGEN-SPECIFIC IMMUNOTHERAPY IN CHILDREN WITH HAY FEVER

    Directory of Open Access Journals (Sweden)

    I. M. Gaiduk

    2013-01-01

    Full Text Available Aims of study: evaluation of immunological parameters in course of sublingual allergen-specific immunotherapy with tree pollen mixture in children with hay fever.Materials and methods: the study included one-hundred patients 5 to 18 years of age with hay fever (pollen rhinitis, rhinoconjunctivitis and/or asthma. Allergen-specific immunotherapy was administered pre-seasonally for three consecutive years. Cytokinechanges were studied in blood serum and in lavages from nasal cavity. Samples assessed before treatment and after 2nd and 3rd courses SLIT completion.Results: increased serum concentrations of IL-10, IFNγ, and decreased IL-4 contents were revealed in the course of treatment. No significant changes in cytokineconcentrations were detectable in nasal lavages.Conclusions: the changes revealed correspond to a shift of T cell response profile towards Th1 pathway, thus confirming pathogenetic effects of sublingual allergen-specific

  5. Distinct modulation of allergic T cell responses by subcutaneous versus sublingual allergen-specific immunotherapy

    DEFF Research Database (Denmark)

    Schulten, Véronique; Tripple, Victoria; Andersen, Kristian Aasbjerg

    2016-01-01

    BACKGROUND: Allergen-specific immunotherapy is the only curative treatment for type I allergy. It can be administered subcutaneously (SCIT) or sublingually (SLIT). The clinical efficacy of these two treatment modalities appears to be similar, but potential differences in the immunological...... mechanisms involved have not been fully explored. OBJECTIVE: To compare changes in the allergen-specific T cell response induced by subcutaneous versus sublingual administration of allergen-specific immunotherapy (AIT). METHODS: Grass pollen allergic patients were randomized into groups receiving either SCIT...... was observed starting 10 months after treatment was commenced. At 24 months, T cell responses showed IL-5 levels significantly below the before treatment baseline. No significant reduction of IL-5 was observed in the SLIT or untreated group. However, a significant transient increase in IL-10 production after...

  6. 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

  7. Rectal and sublingual administration of tacrolimus: a single-dose pharmacokinetic study in healthy volunteers

    Science.gov (United States)

    Stifft, Frank; Vanmolkot, Floris; Scheffers, Ingrid; van Bortel, Luc; Neef, Cees; Christiaans, Maarten

    2014-01-01

    Aims The immunosuppressant tacrolimus is usually administered orally. When this is not feasible, other routes of administration may be useful. Previous research suggested that tacrolimus may be applied sublingually or rectally. Pharmacokinetic data are sparse. The aim of this study was to investigate and compare the pharmacokinetics of these alternative formulations with orally administered tacrolimus. Methods Three single, fixed-dose formulations of tacrolimus were administered in a random sequence in 18 healthy subjects, using a cross-over study design. For sublingual administration, 3 mg of powder obtained from oral capsules was applied under the tongue for a period of 15 min without swallowing, with mouth rinsing afterwards. For rectal administration, a suppository containing 15 mg of the oral powder was used. Oral administration consisted of 7 mg of instant-release tacrolimus capsules (Prograf). Main pharmacokinetic outcome parameters were compared by anova. Results Sublingual administration showed no clinically significant exposure, contrary to rectal administration, where all subjects had clinically relevant exposure, with a lower relative bioavailability (78%), a lower maximal blood concentration and a later time of maximal blood concentration compared with oral administration. Conclusions Sublingual administration of a single dose of tacrolimus does not result in systemic exposure if care is taken not to swallow saliva and to rinse the oral cavity afterwards. Rectal administration of tacrolimus results in clinically relevant systemic exposure and might represent an alternative formulation in case oral administration is not feasible. When used as a topical agent, systemic side-effects should be considered. PMID:24809233

  8. Rigid swelling of sublingual caruncle area due to the salivary gland duct obstruction by a sialolith*

    Science.gov (United States)

    Bernardes Filho, Fred; Martins, Gustavo; Alves, Andreia Oliveira; da Costa, José Ronaldo Vieira; Azulay, David Rubem; Azulay-Abulafia, Luna

    2014-01-01

    Sialolithiasis is the presence of calculus within the ductal system of a salivary gland. Among the diagnostic methods are inspection, palpation, checking the amount of saliva secreted and the identification of a sialolith. The authors present the case of a 37-year-old female patient with edema of the submandibular area and a bulging sublingual caruncle due to a calculus that obstructed the salivary gland ostium. PMID:25387506

  9. Sublingual sugar for hypoglycaemia in children with severe malaria: A pilot clinical study

    Directory of Open Access Journals (Sweden)

    Giani Sergio

    2008-11-01

    Full Text Available Abstract Background Hypoglycaemia is a poor prognostic indicator in severe malaria. Intravenous infusions are rarely feasible in rural areas. The efficacy of sublingual sugar (SLS was assessed in a pilot randomized controlled trial among hypoglycaemic children with severe malaria in Mali. Methods Of 151 patients with presumed severe malaria, 23 children with blood glucose concentrations = 3.3 mmol/l (60 mg/dl within 40 minutes after admission. Secondary outcome measures were early treatment response at 20 minutes, relapse (early and late, maximal BGC gain (CGmax, and treatment delay. Results There was no significant difference between the groups in the primary outcome measure. Treatment response occurred in 71% and 67% for SLS and IVG, respectively. Among the responders, relapses occurred in 30% on SLS at 40 minutes and in 17% on IVG at 20 minutes. There was one fatality in each group. Treatment failures in the SLS group were related to children with clenched teeth or swallowing the sugar, whereas in the IVG group, they were due to unavoidable delays in beginning an infusion (median time 17.5 min (range 3–40. Among SLS, the BGC increase was rapid among the nine patients who really kept the sugar sublingually. All but one increased their BGC by 10 minutes with a mean gain of 44 mg/dl (95%CI: 20.5–63.4. Conclusion Sublingual sugar appears to be a child-friendly, well-tolerated and effective promising method of raising blood glucose in severely ill children. More frequent repeated doses are needed to prevent relapse. Children should be monitored for early swallowing which leads to delayed absorption, and in this case another dose of sugar should be given. Sublingual sugar could be proposed as an immediate "first aid" measure while awaiting intravenous glucose. In many cases it may avert the need for intravenous glucose.

  10. Variability in sublingual microvessel density and flow measurements in healthy volunteers.

    Science.gov (United States)

    Hubble, Sheena M A; Kyte, Hayley L; Gooding, Kim; Shore, Angela C

    2009-02-01

    As sublingual microvascular indices are increasingly heralded as new resuscitation end-points, better population data are required to power clinical studies. This paper describes improved methods to quantify sublingual microvessel flow and density in images obtained by sidestream dark field (SDF) technology in healthy volunteers, including vessels under 10 microm in diameter. Measurements of sublingual capillary density and flow were obtained by recording three 15-second images in 20 healthy volunteers over three days. Two independent observers quantified capillary density by using two methods: total vessel length (mm/mm2) and counting (number/mm). Both intraoral and temporal variabilities within subject and observer reproducibilities were determined by using coefficients of variability and reproducibility indices. For small (1-10 microm), medium (11-20 microm), and large (21-50 microm) diameter, mean vessel density with standard deviations (SDs) in volunteers was 21.3(+/- 4.9), 5.2 (+/- 1.2), and 2.7 (+/- 0.9) mm/mm2, respectively. Also, 94.0 +/- 1.4% of small vessels, 94.5 +/- 1.4% of medium vessels, and 94.5+/- 4.0% of large vessels had continuous perfusion. Within subjects, the means of all measurements over three days varied less than 13, 22, and 35% in small, medium, and large vessels, respectively. Interobserver reproducibility was good, especially for capillary (1-10 microm) density and flow measurements. Our methods of microvessel flow and density quantification have low observer variability and confirm the stability of microcirculatory measurements over time. These results facilitate the development of SDF-acquired sublingual microvascular indices as feasible microperfusion markers in shock resuscitation.

  11. The Proteomes of Human Parotid and Submandibular/Sublingual Gland Salivas Collected as the Ductal Secretions

    OpenAIRE

    Denny, Paul; Hagen, Fred K.; Hardt, Markus; Liao, Lujian; Yan, Weihong; Arellanno, Martha; Bassilian, Sara; Bedi, Gurrinder S.; Boontheung, Pinmannee; Cociorva, Daniel; Delahunty, Claire M.; Denny, Trish; Dunsmore, Jason; Faull, Kym F.; Gilligan, Joyce

    2008-01-01

    Saliva is a body fluid with important functions in oral and general health. A consortium of three research groups catalogued the proteins in human saliva collected as the ductal secretions: 1166 identifications—914 in parotid and 917 in submandibular/sublingual saliva—were made. The results showed that a high proportion of proteins that are found in plasma and/or tears are also present in saliva along with unique components. The proteins identified are involved in numerous molecular processes...

  12. The impact of the site of blood sampling on pharmacokinetic parameters following sublingual dosing to dogs.

    Science.gov (United States)

    Sohlberg, E; Halldin, M M; Annas, A; Königsson, K; Jansson, B; Pehrson, R; Borg, N

    2013-01-01

    Drugs are most commonly administered orally, but some potential drug candidates are not suited for oral administration due to poor absorption, high first pass metabolism or gastrointestinal side effects. The interest for transmucosal dosing for systemic drug delivery is increasing, e.g. buccal, sublingual and nasal routes. The evaluation of the systemic plasma concentration and the derivation of the pharmacokinetic parameters of candidate compounds in preclinical studies are essential for drug development. The effect of site of blood sampling on the measured drug concentration, in both animals and humans, is to some extent known but it is not always taken into consideration in the design of pharmacological and toxicological studies. Blood samples were collected both from leg and jugular veins from beagle dogs following a single sublingual dosing of Compound A in order to determine the impact of different sites of blood sampling on plasma pharmacokinetics. Plasma was prepared by centrifugation and plasma concentrations of Compound A were determined by protein precipitation and liquid chromatography followed by mass spectrometric detection. The pharmacokinetic parameters were calculated by non-compartment methods. Sampling from the jugular vein resulted in higher and more variable exposure during the absorption phase compared to sampling from a leg vein. The plasma exposure in the jugular vein, in terms of C(max), was 4-fold compared to that in the leg vein and an approximately 2-fold bioavailability was observed. The aim of this investigation was to determine the impact of the different sites of blood sampling on assessing systemic plasma exposure and pharmacokinetic parameters for Compound A following sublingual dosing to dogs. The results demonstrate the significant impact that the site of blood sampling has on PK parameters, and raise concerns of using the jugular vein as a site of sampling after sublingual and other transmucosal routes of dosing in the head

  13. Sublingual microcirculatory changes during high-volume hemofiltration in hyperdynamic septic shock patients.

    Science.gov (United States)

    Ruiz, Carolina; Hernandez, Glenn; Godoy, Cristian; Downey, Patricio; Andresen, Max; Bruhn, Alejandro

    2010-01-01

    Previous studies have suggested that high volume hemofiltration (HVHF) may contribute to revert hypotension in severe hyperdynamic septic shock patients. However, arterial pressure stabilization occurs due to an increase in systemic vascular resistance, which could eventually compromise microcirculatory blood flow and perfusion. The goal of this study was to determine if HVHF deteriorates sublingual microcirculation in severe hyperdynamic septic shock patients. This was a prospective, non-randomized study at a 16-bed, medical-surgical intensive care unit of a university hospital. We included 12 severe hyperdynamic septic shock patients (norepinephrine requirements > 0.3 μg/kg/min and cardiac index > 3.0 L/min/m2) who underwent a 12-hour HVHF as a rescue therapy according to a predefined algorithm. Sublingual microcirculation (Microscan for NTSC, Microvision Medical), systemic hemodynamics and perfusion parameters were assessed at baseline, at 12 hours of HVHF, and 6 hours after stopping HVHF. Microcirculatory flow index increased after 12 hours of HVHF and this increase persisted 6 hours after stopping HVHF. A similar trend was observed for the proportion of perfused microvessels. The increase in microcirculatory blood flow was inversely correlated with baseline levels. There was no significant change in microvascular density or heterogeneity during or after HVHF. Mean arterial pressure and systemic vascular resistance increased while lactate levels decreased after the 12-hour HVHF. The use of HVHF as a rescue therapy in patients with severe hyperdynamic septic shock does not deteriorate sublingual microcirculatory blood flow despite the increase in systemic vascular resistance.

  14. [Efficacy of the dust mites drops sublingual immunotherapy in pediatric allergic rhinitis].

    Science.gov (United States)

    Xie, Lisheng; Jiang, Yinzhu; Li, Qi

    2016-03-01

    To observe the role of the dust mites drops sublingual immunotherapy(SLIT) in pediatric allergic rhiriitis caused by dust mites and compare its efficacy between monosensitized and polysensitized children. A total of 77 pediatric allergic rhinitis patients received Dermatophagoides farina extracts sublingual immunotherapy for 2 years were enrolled as desensitization group and were allocated into monosensitized group (41 cases) and polysensitized group (36 cases) according to the number of coexisting allergens. Meanwhile another 33 allergic rhinitis children treated by pharmacotherapy during the period were collected as control group. The total symptom scores (TNSS), total medication scores (TMS) and visual analogue scale(VAS) were assessed at the beginning, six months, 1 year and 2 years of the treatment. SPSS 13. 0 software was used to analyze the data. the score of TNSS and VAS in desensitization was slightly higher than the control after six months treatment, but without difference at l year and 2 years; the score of TMS had significantly improved in desensitization compared with the corresponding points in control. All the parameters in monosensitized group were equivalent with polysensitizend group, except the score of TMS was slightly lower than the polysensitizend group at six months. Dust mite drops sublingual immunotherapy is effective for the allergic rhinitis children caused by mites. And it has similar immunotherapy efficacy between monosensitized and polysensitized children.

  15. Hyperoxia does not affect oxygen delivery in healthy volunteers while causing a decrease in sublingual perfusion.

    Science.gov (United States)

    Smit, B; Smulders, Y M; Eringa, E C; Gelissen, H P M M; Girbes, A R J; de Grooth, H J S; Schotman, H H M; Scheffer, P G; Oudemans-van Straaten, H M; Spoelstra-de Man, A M E

    2017-12-06

    To determine the human dose-response relationship between a stepwise increase in arterial oxygen tension and its associated changes in oxygen delivery and sublingual microcirculatory perfusion METHODS: Fifteen healthy volunteers breathed increasing oxygen fractions for 10 minutes to reach arterial oxygen tensions of baseline (breathing air), 20 kPa, 40 kPa, 60 kPa and max kPa (breathing oxygen). Systemic hemodynamics were measured continuously by the volume-clamp method. At the end of each period, the sublingual microcirculation was assessed by Sidestream Darkfield Imaging RESULTS: Systemic oxygen delivery was unchanged throughout the study (Pslope =0.8). Perfused vessel density decreased in a sigmoidal fashion (max -15% while breathing oxygen, SD18, Pslope =0.001). Cardiac index decreased linearly (max -10%, SD10, Pslope <0.001) due to a reduction in heart rate (max -10%, SD7, Pslope =0.009). There were no changes in stroke volume or mean arterial pressure. Most changes became apparent above an arterial oxygen tension of 20 kPa CONCLUSIONS: In healthy volunteers, supraphysiological arterial oxygen tensions have no effect on systemic oxygen delivery. Sublingual microcirculatory perfused vessel density decreased in a dose-dependent fashion. All hemodynamic changes appear negligible up to an arterial oxygen tension of 20 kPa This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Sublingual Nucleotides Prolong Run Time to Exhaustion in Young Physically Active Men

    Directory of Open Access Journals (Sweden)

    Sergej M. Ostojic

    2013-11-01

    Full Text Available Although dietary nucleotides have been determined to be required for normal immune function, there is limited direct interventional evidence confirming performance-enhancing effects of sublingual nucleotides in humans. A double-blind, placebo-controlled, randomized trial was conducted to evaluate the effect of sublingual nucleotides (50 mg/day administered for 14 days in thirty young healthy physically active males, on endurance performance and immune responses. Fasting white blood cell count, natural killer cells (NKC number, NKC cytotoxic activity, and serum immunoglobulin (IgA, IgM, IgG, and time to exhaustion, peak rate of perceived exertion, peak heart rate, and peak running speed during the exercise test were measured at baseline (day 0 and post-intervention (day 14. Time to exhaustion, as well as serum immunoglobulin A and NKC cytotoxic activity, were significantly higher at day 14 (p < 0.05 in participants supplemented with nucleotides compared with those who consumed placebo. No significant differences in other parameters were observed between groups at post-intervention. No volunteers withdrew before the end of the study nor reported any vexatious side effects of supplementation. The results of the present study suggest that sublingual nucleotides may provide pertinent benefit as both an ergogenic and immunostimulatory additive in active males.

  17. Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial.

    Science.gov (United States)

    Lima, M Torres; Wilson, D; Pitkin, L; Roberts, A; Nouri-Aria, K; Jacobson, M; Walker, S; Durham, S

    2002-04-01

    Previous studies suggest that sublingual immunotherapy (SLIT) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed. To evaluate the efficacy and safety of SLIT in grass pollen-induced seasonal rhinoconjunctivitis. A randomized, placebo-controlled trial in 56 adults over 18 months. Outcome measures included diary scores of seasonal symptoms and medication use, overall assessments, conjunctival and intradermal provocation tests and serum antibody measurements. To investigate possible mechanisms, sublingual biopsies were taken for measurement of local T cells, antigen-presenting cells and IL-12 mRNA expression. There were no significant differences between the immunotherapy (IT) and placebo groups for diary symptom scores (P = 0.48) or rescue medication (P = 0.19). The patients' overall assessment of hayfever severity compared with previous years showed a highly significant improvement in favour of the IT group (P pollen sublingual immunotherapy was well tolerated. Although there was no significant change in diary scores, the improvement in overall assessments, which correlated with inhibition of the late skin response and increases in serum IgG4 : IgE ratio, indicates the need for larger, dose-ranging studies.

  18. 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

  19. 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.

  20. Development and Evaluation of Mucoadhesive Chlorhexidine Tablet ...

    African Journals Online (AJOL)

    Erah

    Purpose: To formulate mucoadhesive chlorhexidine tablets and evaluate their drug release characteristics and mechanism. Methods: Chlorhexidine buccal adhesive tablets were prepared by direct compression using a blend of hydroxypropyl methylcellulose (HPMC) and chitosan as the bioadhesive polymers.

  1. Development and evaluation of miconazole mucoadhesive tablets ...

    African Journals Online (AJOL)

    Purpose: To develop mucoadhesive tablets containing miconazole (MCZ) for the treatment of oropharyngeal candidiasis, using chitosan and hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Methods: Mucoadhesive tablets were formulated and optimized using a 23 factorial design and direct ...

  2. Development and evaluation of miconazole mucoadhesive tablets ...

    African Journals Online (AJOL)

    Purpose: To develop mucoadhesive tablets containing miconazole (MCZ) for the treatment of oropharyngeal candidiasis, using chitosan and hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Methods: Mucoadhesive tablets were formulated and optimized using a 23 factorial design and direct.

  3. Preparation and Evaluation of Orodispersible Tablets Containing ...

    African Journals Online (AJOL)

    Purpose: To formulate simvastatin orodispersible tablets with high dissolution rate and enhanced bioavailability. ... DSC and FTIR indicated the formation of solid dispersion without chemical interaction between simvastatin and polymer. Orodispersible tablet prepared with Emcosoy and Pullulan showed least wetting and.

  4. Attitudes towards Smart Phones and Tablets

    National Research Council Canada - National Science Library

    Ali Akbar Ansarin; Farahman Farrokhi; Hamid Reza Mahboudi; Zohreh Adeli Jam

    2017-01-01

    This paper examines the perceptions of advantages of smart phones and tablets on basic and general English students' language learning, self-sufficiency, and interest using smart phones and tablets...

  5. Tablet Analysis Using Gravimetric Dilutions

    Science.gov (United States)

    Simonson, Larry A.

    2001-10-01

    This experiment introduces the concept of gravimetric dilutions in the context of tablet analysis. Caffeine tablets are analyzed by absorbance at 274 nm with reference to a standard calibration graph and tested for compliance with the USP criterion. All samples and standards are prepared using gravimetric dilutions without reference to volume or density. This experiment is appropriate for high school and college freshman chemistry courses and may be useful at higher levels. It is only necessary that students have had exposure to Beer's law.

  6. Touch Screen Tablets and Emergent Literacy

    Science.gov (United States)

    Neumann, Michelle M.; Neumann, David L.

    2014-01-01

    The use of touch screen tablets by young children is increasing in the home and in early childhood settings. The simple tactile interface and finger-based operating features of tablets may facilitate preschoolers' use of tablet application software and support their educational development in domains such as literacy. This article reviews…

  7. Optimization of Formulations of Metoprolol Succinate Tablets ...

    African Journals Online (AJOL)

    Background: Release-retarding polymers in matrix tablets play a vital role in controlling drug release from tablets. Objectives: To prepare metoprolol succinate tablets by direct compression using Ofada rice (Oryza glaberrima Steud) starch acetate, degree of substitution (DS) 2.22, as a matrix for sustained release. Materials ...

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  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. 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

  20. Randomized double-blind placebo-controlled trial of sublingual immunotherapy in children with house dust mite allergy in primary care: Study design and recruitment

    NARCIS (Netherlands)

    C.M.A. de Bot (Cindy); H. Moed (Heleen); M.Y. Berger (Marjolein); E. Röder (Esther); H. de Groot (Hans); J.C. de Jongste (Johan); R. Gerth van Wijk (Roy); J.C. van der Wouden (Hans)

    2008-01-01

    textabstractBackground. For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A

  1. Randomized double-blind placebo-controlled trial of sublingual immunotherapy in children with house dust mite allergy in primary care : study design and recruitment

    NARCIS (Netherlands)

    de Bot, Cindy M. A.; Moed, Heleen; Berger, Marjolein Y.; Roder, Esther; de Groot, Hans; de Jongste, Johan C.; van Wijk, Roy Gerth; van der Wouden, Johannes C.

    2008-01-01

    Background: For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A randomized

  2. 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

  3. 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.

  4. 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

  5. Learning, Tablet, Culture-Coherence?

    Science.gov (United States)

    Norqvist, Lars

    2016-01-01

    This paper presents understandings of learning in schools where Internet-enabled Information and Communication Technologies (ICTs) are taken for granted. The context is a full-scale 1:1 tablet project in Danish municipality schools where this study bring forward expressions of learning from one class (12-13 year old children) in order to offer…

  6. 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.

  7. 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

  8. The efficacy of sublingual immunotherapy for respiratory allergy is not affected by different dosage regimens in the induction phase.

    Science.gov (United States)

    Sambugaro, R; Puccinelli, P; Burastero, S E; Di Rienzo, V

    2003-01-01

    Sublingual administration of allergens is a safe and effective alternative to subcutaneous immunotherapy in patients with respiratory allergies. A drawback to this therapeutic approach is the relatively long and complex management of the induction phase. To determine whether different induction regimens affect the outcome of sublingual immunotherapy. Adult and pediatric patients with allergic rhinoconjunctivitis and/or asthma were included in the study. Ten subjects served as controls and received symptomatic treatments. Forty-three subjects were allocated to sublingual immunotherapy, with three different induction protocols (8-, 15- and 20-day, respectively). Symptom and medication scores, skin test results and (in asthmatic patients) FEV1 values were monitored for two years. Adverse effects were recorded. All induction regimens produced a significant improvement in symptom and medication usage (p protocol is safe and effective. Our results encourage the usage of shorter induction regimens, which produce better compliance with this therapy.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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...

  17. 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

  18. In vitro and in vivo evaluation of a sublingual fentanyl wafer formulation

    Directory of Open Access Journals (Sweden)

    Lim SCB

    2013-04-01

    Full Text Available Stephen CB Lim,1,3 Michael J Paech,2 Bruce Sunderland,3 Yandi Liu3 1Pharmacy Department, Armadale Health Service, Armadale, 2School of Medicine and Pharmacology, University of Western Australia, and Department of Anaesthesia and Pain Medicine, King Edward Memorial Hospital for Women, Subiaco, 3School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia Background: The objective of this study was to prepare a novel fentanyl wafer formulation by a freeze-drying method, and to evaluate its in vitro and in vivo release characteristics, including its bioavailability via the sublingual route. Methods: The wafer formulation was prepared by freeze-drying an aqueous dispersion of fentanyl containing sodium carboxymethylcellulose and amylogum as matrix formers. Uniformity of weight, friability, and dissolution testing of the fentanyl wafer was achieved using standard methods, and the residual moisture content was measured. The fentanyl wafer was also examined using scanning electron microscopy and x-ray diffraction. The absolute bioavailability of the fentanyl wafer was evaluated in 11 opioid-naïve adult female patients using a randomized crossover design. Results: In vitro release showed that almost 90% of the fentanyl dissolved in one minute. In vivo, the first detectable plasma fentanyl concentration was observed after 3.5 minutes and the peak plasma concentration between 61.5 and 67 minutes. The median absolute bioavailability was 53.0%. Conclusion: These results indicate that this wafer has potential as an alternative sublingual fentanyl formulation. Keywords: absolute bioavailability, fentanyl wafer, in vitro dissolution, in vivo study, pharmacokinetics, sublingual

  19. Airway function indicators and blood indicators in children with dust mite allergic rhinitis after sublingual immunotherapy

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    Hua Xiang

    2016-07-01

    Full Text Available Objective: To evaluate the airway function indicators and blood indicators in children with dust mite allergic rhinitis after sublingual immunotherapy. Methods: A total of 68 children with dust mite allergic rhinitis treated in our hospital from November, 2012 to October, 2015 were selected as the research subjects and randomly divided into observation group 34 cases and control group 34 cases. The control group received clinical routine therapy for allergic rhinitis, the observation group received sublingual immunotherapy, and then differences in basic lung function indicator values, small airway function indicator values and levels of serum inflammatory factors as well as serum ECP, TARC, Eotaxin-2 and VCAM were compared between two groups after treatment. Results: The FVC, FEV1, PEF and FEV1/FVC values of the observation group after treatment were higher than those of the control group (P<0.05; the MMEF, MEF50% and MEF25% values of the observation group were higher than those of the control group, and the proportion of AHR was lower than that of the control group (P<0.05; the serum IL-4, IL-9, IL-12, IL-13 and IL-16 levels of the observation group after treatment were lower than those of the control group, and the IL-10 and IL-12 levels are higher than those of the control group (P<0.05; the serum ECP, TARC, Eotaxin-2 and VCAM levels of the observation group children after treatment were lower than those of the control group (P<0.05. Conclusions: Sublingual immunotherapy for children with dust mite allergic rhinitis can optimize the airway function, reduce the systemic inflammatory response and eventually improve the children’s overall state, and it’s has positive clinical significance.

  20. ROLE OF 400 MCG INTRAOPERATIVE SUBLINGUAL MISOPROSTOL FOR REDUCTION OF CAESAREAN BLOOD LOSS

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    Lalmohan Nayak

    2017-02-01

    Full Text Available BACKGROUND Lower segment caesarean section is a common surgical procedure. Postpartum haemorrhage incidence after LSCS is 4%. Misoprostol is a prostaglandin E1 analogue with good uterotonic properties, easy availability, low cost, thermostability, long shelf life, easy administration and few adverse effects at therapeutic dose. It is readily absorbed by oral, sublingual, buccal, vaginal or rectal route. Sublingual route attains quickest concentration. Dose of 400 mcg was chosen in this study to minimise adverse effects with optimal therapeutic benefit. The aim of the study is to determine the efficacy of sublingual misoprostol in reducing caesarean blood loss. MATERIALS AND METHODS It is a prospective experimental study done in VSSIMSAR, Burla. Women undergoing LSCS were randomly assigned to study and control groups of equal strength of 100 each. In all cases, preoperative Hb%, haematocrit, pulse, BP was noted. Study group were given 400 mcg misoprostol at the time of cord clamping. In control group, nothing was given. In all patients, active management of third stage of labour was done by using oxytocin 10 IU (IV along with uterine massage. Blood loss soaked by tetra was calculated using formula, blood loss = wet weight-dry weight/1.05 (1.05 is constant. Amount of blood loss, postoperative Hb%, haematocrit, pulse rate, BP was noted in both groups and compared. BP and pulse were noted after 1 hour and Hb%, haematocrit were noted after 24 hours. RESULTS Study group showed significant decrease in total blood loss (around 117.9 mL as compared to control group. There was significant decrease in the postoperative fall in Hb in the study group as compared to control, the mean difference being 0.631 gm%. Study group also showed decrease in postoperative fall in haematocrit as compared to control, the mean difference being 0.055. CONCLUSION Misoprostol significantly reduced caesarean blood loss and doesn’t affect foetal outcome without significant

  1. Ultrastructural changes in the sublingual salivary gland of prenatal buffalo (Bubalus bubalis

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    A. D. Singh

    2016-03-01

    Full Text Available Aim: The present study was aimed to elucidate ultrastructural changes in the development of sublingual salivary gland of buffalo during prenatal life. Materials and Methods: The study was carried out on sublingual salivary gland of 36 buffalo fetuses ranging from 13.2 cm curved crown-rump length (CVRL (88th day to full term. The fetuses were categorized into three groups based on their CVRL. Results: The cells lining the terminal tubules were undifferentiated with poorly developed cytoplasmic organelles but lacked secretory granules (SGs at 13.2 cm CVRL (88th day. The SGs appeared first in the form of membrane-bound secretory vesicles with homogeneous electron-dense as well as electron-lucent contents at 21.2 cm CVRL (122nd day; however, mucous acinar cells contained electron-lucent granules, while serous secretory cells as well as serous demilunes showed electron-dense granules at 34 cm CVRL (150th day of prenatal life. At 53.5 cm CVRL (194th day, both mucous and serous acini were differentiated by the density of SGs. Conclusion: The cytoplasm of acinar cells was filled with mitochondria, rough endoplasmic reticulum, and Golgi profiles in mid and late fetal age groups. The SGs were increased in number during the late fetal age group. The myoepithelial cells (MECs were located at the base of the acinar cells as well as intercalated and striated ducts and were stellate in shape. The ultrastructure of MEC revealed a parallel stream of myofilaments in the cytoplasm and its processes. The mucous cells were predominantly present in the sublingual salivary gland and were pyramidal in shape.

  2. Adverse reaction to sublingual Parietaria vaccine following an ultra-rush induction.

    Science.gov (United States)

    Scala, G; Ciccarelli, A; Calabrò, C

    2014-05-01

    In the treatment of respiratory allergies Sublingual Immunotherapy (SLIT) represents a valid alternative to Subcutaneous Immunotherapy (SCIT) for its better safety profile. We describe a case of acute severe asthma following the first maintenance dose of SLIT in a boy allergic to Parietaria pollen. At the initiation of therapy, the patient was in healthy condition and his asthma appeared to be under control. An ultra-rush induction had given no reaction. Despite the good safety profile of SLIT, clinicians should be aware of the risk of adverse effects when prescribing SLIT for respiratory allergies.

  3. Sublingual misoprostol versus intravenous oxytocin in the management of postpartum hemorrhage

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    Beigi A

    2009-11-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Postpartum hemorrhage is a major cause of maternal mortality and morbidity. It has been identified that active management of third stage of labor is an effective way in preventing postpartum hemorrhage. This randomized controlled trial was conducted to compare sublingual misoprostol versus intravenous oxytocin in the management of postpartum hemorrhage in nulliparous women."n"nMethods: In this randomized controlled trial conducted in Arash hospital from 2006 to 2009, Five hundred forty two nulliparous pregnant women were enrolled. They were randomized to receive either 400 microgram sublingual misoprostol or 20 IU oxytocin intravenously, immediately after the birth of newborn. "n"nResults: Post partum Hemorrhage was significantly lower in women who received sublingual misoprostol (p<0.0001. Patients who received misoprostol had shorter length of third stage of labor (6.45 minute in misoprostol Vs 6.9 minute in oxytocin group, p=0.003. Comparison of hemoglobin levels in two groups before and after delivery showed that there is a significant lesser hemoglobin drop in misoprostol group p=0.046. Side effects were more common in misoprostol group (p<0.0001. However, they were not serious; shivering (35.66% in

  4. A Rare Primary Neuroendocrine Tumor (Typical Carcinoid of the Sublingual Gland

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    Kenji Yamagata

    2016-01-01

    Full Text Available A typical carcinoid is extremely rare in the oral cavity. We here present a case of a typical carcinoid arising in the sublingual gland of a 62-year-old woman. The tumor was removed by primary excision with 10 mm surgical margins and submandibular dissection. Examination of the tumor showed medium-sized tumor cells that were positive for CD56 and chromogranin A, with no necrosis, and with a mitotic count less than 1/10 HPF. A pathological diagnosis of typical carcinoid was made from both morphological and immunological examinations. One year after excision surgery, there was no tumor recurrence or neck metastasis.

  5. Distinct modulation of allergic T cell responses by subcutaneous versus sublingual allergen-specific immunotherapy

    DEFF Research Database (Denmark)

    Schulten, Véronique; Tripple, Victoria; Andersen, Kristian Aasbjerg

    2016-01-01

    mechanisms involved have not been fully explored. OBJECTIVE: To compare changes in the allergen-specific T cell response induced by subcutaneous versus sublingual administration of allergen-specific immunotherapy (AIT). METHODS: Grass pollen allergic patients were randomized into groups receiving either SCIT......: The most dominant immunological changes on a cellular level was a decrease in IL-5 in the SCIT group and a significant, transient increase of IL-10 observed after 10 months of treatment in both treated groups. The distinct routes of AIT administration may induce different immune-modulatory mechanisms...

  6. Pharmaceutical and analytical evaluation of triphalaguggulkalpa tablets

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    Shreeram S Savarikar

    2011-01-01

    Full Text Available Aim of the Study: Development of standardized, synergistic, safe and effective traditional herbal formulations with robust scientific evidence can offer faster and more economical alternatives for the treatment of disease. The main objective was to develop a method of preparation of guggulkalpa tablets so that the tablets meet the criteria of efficacy, stability, and safety. Materials and Methods: Triphalaguggulkalpa tablet, described in sharangdharsanhita and containing guggul and triphala powder, was used as a model drug. Preliminary experiments on marketed triphalaguggulkalpa tablets exhibited delayed in vitro disintegration that indicated probable delayed in vivo disintegration. The study involved preparation of triphalaguggulkalpa tablets by Ayurvedic text methods and by wet granulation, dry granulation, and direct compression method. The tablets were evaluated for loss on drying, volatile oil content, % solubility, and steroidal content. The tablets were evaluated for performance tests like weight variation, disintegration, and hardness. Results: It was observed that triphalaguggulkalpa tablets, prepared by direct compression method, complied with the hardness and disintegration tests, whereas tablets prepared by Ayurvedic text methods failed. Conclusion: Direct compression is the best method of preparing triphalaguggulkalpa tablets.

  7. Dose Uniformity of Scored and Unscored Tablets: Application of the FDA Tablet Scoring Guidance for Industry.

    Science.gov (United States)

    Ciavarella, Anthony B; Khan, Mansoor A; Gupta, Abhay; Faustino, Patrick J

    This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units , which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. Tablet splitting has become a very common practice in the United States and throughout the

  8. 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

  9. 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.

  10. 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.

  11. Stability study of Raloxifene tablets

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    Jorge Enrique Rodríguez Chanfrau

    Full Text Available Introduction: Raloxifene is a selective estrogen receptor modulator from the benzothiophene family. Several clinical trials have shown that raloxifene reduces bone loss rate in the spinal column and may increase bone mass at certain sites. Objective: to determine the physical and chemical stabilities of raloxifene tablets. Methods. three pilot scale batches of 5 kg each were prepared. In vitro dissolution, chemical stability, photostability and humidity studies were carried out. Samples were collected at 0, 1, 2, 3 and 6 months for the accelerated stability study and at 0, 6, 12, 18 and 24 months for the shelf life stability study. Chemical stability was determined using high performance liquid chromatography analytical method, which was developed and validated prior to the study. Results: in the accelerated stability study, the percentages of dissolved drug were more than 90 % and drug content porcentages were between 90 % and 110 %. Humidity conditions affected the chemical stability of the tablets. Conclusions: All raloxifene tablet batches formulations were stable for 24 months in the studied containers stored at 32 ± 2 ºC and waterproof. In vitro drug release dissolution showed good results for 24 months.

  12. Can Tablet Computers Enhance Faculty Teaching?

    Science.gov (United States)

    Narayan, Aditee P; Whicker, Shari A; Benjamin, Robert W; Hawley, Jeffrey; McGann, Kathleen A

    2015-06-01

    Learner benefits of tablet computer use have been demonstrated, yet there is little evidence regarding faculty tablet use for teaching. Our study sought to determine if supplying faculty with tablet computers and peer mentoring provided benefits to learners and faculty beyond that of non-tablet-based teaching modalities. We provided faculty with tablet computers and three 2-hour peer-mentoring workshops on tablet-based teaching. Faculty used tablets to teach, in addition to their current, non-tablet-based methods. Presurveys, postsurveys, and monthly faculty surveys assessed feasibility, utilization, and comparisons to current modalities. Learner surveys assessed perceived effectiveness and comparisons to current modalities. All feedback received from open-ended questions was reviewed by the authors and organized into categories. Of 15 eligible faculty, 14 participated. Each participant attended at least 2 of the 3 workshops, with 10 to 12 participants at each workshop. All participants found the workshops useful, and reported that the new tablet-based teaching modality added value beyond that of current teaching methods. Respondents developed the following tablet-based outputs: presentations, photo galleries, evaluation tools, and online modules. Of the outputs, 60% were used in the ambulatory clinics, 33% in intensive care unit bedside teaching rounds, and 7% in inpatient medical unit bedside teaching rounds. Learners reported that common benefits of tablet computers were: improved access/convenience (41%), improved interactive learning (38%), and improved bedside teaching and patient care (13%). A common barrier faculty identified was inconsistent wireless access (14%), while no barriers were identified by the majority of learners. Providing faculty with tablet computers and having peer-mentoring workshops to discuss their use was feasible and added value.

  13. Measuring tablet porosity using multispectral imaging system

    Science.gov (United States)

    Nippolainen, Ervin; Ervasti, Tuomas; Ketolainen, Jarkko; Kamshilin, Alexei A.

    2010-05-01

    A multispectral imaging system with computer controlled light source of 16 light emitting diodes is applied for measuring of tablet porosity. The system is based on a subspace vector model of surface reflection. The measured spectral data are compressed on the stage of measurement and used directly for the discrimination of tablets with different porosity. The experimental results demonstrate that the multispectral imaging system is a potential method for tablet porosity measurement.

  14. Congenital hypothyroidism due to ectopic sublingual thyroid gland in Prader-Willi Syndrome: a case report.

    Science.gov (United States)

    Bocchini, Sarah; Fintini, Danilo; Grugni, Graziano; Boiani, Arianna; Convertino, Alessio; Crinò, Antonino

    2017-09-22

    Thyroid gland disorders are variably associated with Prader-Willi syndrome (PWS). Many of the clinical features in newborns with PWS are similar to those found in congenital hypothyroidism (CH). We report a case of a girl with CH and PWS. At the age of 9 months CH caused by an ectopic sublingual thyroid was diagnosed, and hormone replacement therapy was started. In spite of this treatment a decrease in growth velocity, weight excess and delayed development were observed. At the age of 9 years PWS was suspected on the basis of phenotype and genetic tests confirmed a maternal uniparental disomy of chromosome 15. This is the second reported case of hypothyroidism due to an ectopic sublingual thyroid gland in PWS suggesting that, although rare, an association between CH and PWS may exist. In our case diagnosis of PWS was delayed because mental retardation, hypotonia, obesity and short stature were initially attributed to hypothyroidism. In this context PWS should be considered in obese children with CH who do not improve adequately with l-thyroxine therapy. Also, thyroid function in all PWS children should be assessed regularly in order to avoid delayed diagnosis of hypothyroidism.

  15. Acinar autolysis and mucous extravasation in human sublingual glands: a microscopic postmortem study

    Directory of Open Access Journals (Sweden)

    Luciana Reis AZEVEDO-ALANIS

    2015-10-01

    Full Text Available Although some morphological investigations on aged human sublingual glands (HSG found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated.Objective The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death.Material and Methods 186 cadavers’ glands were allocated to age groups: I (0–30 years; II (31–60, and III (61–90. Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM. Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05.Results There was correlation between age and acinar autolysis (r=0.38; p=0.0001. However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis.Conclusion Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death.

  16. Spontaneous sublingual and intramural small-bowel hematoma in a patient on oral anticoagulation

    Directory of Open Access Journals (Sweden)

    Mohamed Moftah

    2012-08-01

    Full Text Available Spontaneous sublingual hematoma and intramural small bowel hematoma are rare and serious complications of anticoagulant therapy. Though previously reported individually, there has been no previous report of the same two complications occurring in a single patient. A 71-year-old Caucasian man, who was on warfarin for atrial fibrillation, presented with difficulty in swallowing due to a sublingual hematoma. He was observed in our intensive care unit, his warfarin was held and he recovered with conservative management. He represented two months later with a two day history of abdominal pain and distension. An abdominopelvic computed tomography (CT scan now showed small bowel obstruction due to intramural small bowel hematoma and haemorrhagic ascites. Again, this was treated expectantly with a good outcome. In conclusion, life threatening haemorrhagic complications of oral anticoagulant therapy can recur. Conservative treatment is successful in most cases, but an accurate diagnosis is mandatory to avoid unnecessary surgery. CT scan is the investigation of choice for the diagnosis of suspected haemorrhagic complications of over coagulation.

  17. In vitro and in vivo evaluation of a sublingual fentanyl wafer formulation

    Science.gov (United States)

    Lim, Stephen CB; Paech, Michael J; Sunderland, Bruce; Liu, Yandi

    2013-01-01

    Background The objective of this study was to prepare a novel fentanyl wafer formulation by a freeze-drying method, and to evaluate its in vitro and in vivo release characteristics, including its bioavailability via the sublingual route. Methods The wafer formulation was prepared by freeze-drying an aqueous dispersion of fentanyl containing sodium carboxymethylcellulose and amylogum as matrix formers. Uniformity of weight, friability, and dissolution testing of the fentanyl wafer was achieved using standard methods, and the residual moisture content was measured. The fentanyl wafer was also examined using scanning electron microscopy and x-ray diffraction. The absolute bioavailability of the fentanyl wafer was evaluated in 11 opioid-naïve adult female patients using a randomized crossover design. Results In vitro release showed that almost 90% of the fentanyl dissolved in one minute. In vivo, the first detectable plasma fentanyl concentration was observed after 3.5 minutes and the peak plasma concentration between 61.5 and 67 minutes. The median absolute bioavailability was 53.0%. Conclusion These results indicate that this wafer has potential as an alternative sublingual fentanyl formulation. PMID:23596347

  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. 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.

  1. 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

  2. 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.

  3. 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).

  4. 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…

  5. Mucoadhesive tablets for controlled release of acyclovir.

    Science.gov (United States)

    Ruiz-Caro, Roberto; Gago-Guillan, Manuel; Otero-Espinar, Francisco Javier; Veiga, María Dolores

    2012-01-01

    Mucoadhesive chitosan (CS) and/or hydroxypropyl-methylcellulose (HPMC) tablets for gastric drug delivery of acyclovir (ACV) have been developed in order to improve the ACV oral bioavailability. Swelling, bioadhesive and dissolution studies were carried out in two acidic media (pH 1.5 and 4) in order to determine the tablets behaviour in both fed and fasted states. All the designed tablets showed good mucoadhesive properties on gastric mucosa due to the presence of CS and/or HPMC. In vitro dissolution of ACV from tablets was influenced by the swelling behaviour of each polymer. All data release of the studied tablets fitted to Hopfenberg model, which describes drug release from tablets displaying heterogeneous erosion. HPMC and CS/HPMC tablets revealed a sustained release for 24 h, but a complete dissolution of the tablets was not produced at this time. On the contrary, tablets which contained only CS as polymer were able to release the total amount of ACV for 4 h, due to the CS imbibition and erosion processes in pH 1.5 medium. These results allowed us to conclude that CS is the excipient to be chosen to obtain gastroretentive formulations, due to its demonstrated gastric compatibility.

  6. Tablet surface characterisation by various imaging techniques

    DEFF Research Database (Denmark)

    Seitavuopio, Paulus; Rantanen, Jukka; Yliruusi, Jouko

    2003-01-01

    The aim of this study was to characterise tablet surfaces using different imaging and roughness analytical techniques including optical microscopy, scanning electron microscopy (SEM), laser profilometry and atomic force microscopy (AFM). The test materials compressed were potassium chloride (KCl......) and sodium chloride (NaCl). It was found that all methods used suggested that the KCl tablets were smoother than the NaCl tablets and higher compression pressure made the tablets smoother. Imaging methods like optical microscopy and SEM can give useful information about the roughness of the sample surface...

  7. Formulation development of carvedilol compression coated tablet.

    Science.gov (United States)

    Shah, Ritesh; Patel, Sachin; Patel, Hetal; Pandey, Sonia; Shah, Shailesh; Shah, Dinesh

    2013-01-01

    The aim of present research was to produce carvedilol compression coated tablet to provide biphasic drug release. A compressed coated tablet made of a sustained release core tablet and an immediate release coat tablet. Both the core and the coat contained carvedilol. The sustained release effect was achieved with polymers (HPMC K4M and PEO WSR 205) to modulate the release of the drug. The powder blends for core and coat tablets were evaluated for angle of repose, bulk density, compressibility index, and drug content. Compressed coated tablets were evaluated for thickness, diameter, weight variation test, drug content, hardness, friability, disintegration and in vitro release studies. The powder blends showed satisfactory flow properties, compressibility, drug content and all the tablet formulations showed acceptable pharmaco-technical properties. Carvedilol contained in the fast releasing component was released within 3 min, whereas the drug in the core tablet was released at different times up to 24 h, depending on the composition of the matrix tablet. The mechanism of drug release was fickian diffusion or anomalous behavior. Batch F7, containing 10 mg PEO WSR 205 and 5 mg HPMC K4M, showed maximum similarity with theoretical profile and zero order drug release kinetic.

  8. A randomized controlled trial and novel mathematical analysis of the analgesic effect of oxycodone versus paracetamol orodispersible tablets.

    Science.gov (United States)

    Martini, C H; Proto, P; Olofsen, E; van Velzen, M; Aarts, L; Dahan, A; Niesters, M

    2015-03-01

    For effective treatment of acute pain, a rapid onset of action is important. Here we quantify the antinociceptive profile of an orodispersible oxycodone tablet (OOT) in a randomized, double-blind, active comparator (paracetamol orodispersible tablet, POT), crossover study design in a population of healthy volunteers. Twelve female volunteers were randomized to receive 20 mg OOT and 500 mg POT sublingually on two occasions. The electrical pain threshold (EPTh), electrical pain tolerance (EPTol) and pressure pain threshold (PPT) were obtained at regular intervals for 5 h. Time-response data were analysed with a longitudinal pharmacodynamic model characterized by rate constants for analgesia onset (kON ), offset (kOFF ), potency parameter (EFF) and validated with a bootstrap analysis. Values are the median (95% CI) as derived from the bootstrap analysis. OOT produced a rapid increase in response values. For electrical pain analgesia onset, t½kON , 44 (25-67) versus analgesia offset, t½kOFF , 156 (63-552) min, p mathematical model of analgesia evolution. This method allows quantification of a variety of responses times from sparse data sets. Response times as defined by a 30% increase in response thresholds varied significantly among end points: EPTol 15 min, PPTh 18 min and EPTh 41 min. © 2014 European Pain Federation - EFIC®

  9. Safety, tolerability and clinical efficacy of ultra-rush sublingual immunotherapy among patients suffering from allergic rhinitis.

    Science.gov (United States)

    Balaji, R; Parasuramalu, B G; Chandregowda, B V; Gangaboraiah

    2014-01-01

    Conventional immunotherapy for allergy with 3-5 years of treatment period has poor compliance. Ultra-rush sublingual immunotherapy with a shorter period of treatment can have better compliance. There are very few studies on ultra-rush sublingual immunotherapy all over the world. (1) To determine allergen sensitivity among allergic rhinitis patients. (2) To assess safety, tolerability and clinical efficacy of ultra-rush sublingual immunotherapy. The present study was conducted in Allergy clinic, KIMS Hospital & Research Centre, Bangalore, India from January 2010 to June 2011. After obtaining Institutional Ethics Committee approval, 40 allergic rhinitis patients (according to ARIA guidelines) in the 18-60 years age group who were positive for aeroallergens in skin prick test were recruited for ultra-rush sublingual immunotherapy (20min initial phase and 4-month maintenance phase) and followed for 8 months with symptom and treatment diary. Out of 40 patients, the majority, 36 (90.00%) patients were sensitive to house dust mites. Six patients had seven immediate adverse reactions and seven patients had eight delayed adverse reactions. All subsided without medication or with symptomatic oral medications. All patients tolerated ultra-rush SLIT and there was significant decrease in both symptom-score and treatment received in these patients. Ultra-rush SLIT regimen has excellent safety, tolerability and clinical efficacy among allergic rhinitis patients. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.

  10. Comparing vaginal and sublingual administration of misoprostol for labour induction in women with intra-uterine fetal death.

    NARCIS (Netherlands)

    Geels, Y.P.; Gouberville, M.C. de; Visser, L.; Asten, H.A.G.H. van

    2010-01-01

    The objective of this study was to compare complications and effectiveness of induction after vaginal and sublingual administration of misoprostol for labor induction in women with intra-uterine fetal death (IUFD). In a district hospital in Ghana, 23 women with IUFD who underwent labor induction

  11. Matrix release from tablets prepared with aqueous dispersion of an ...

    African Journals Online (AJOL)

    . Resulting granules were compressed to 500 mg tablets using a single punch machine. The tablets were subjected to hardness, friability, disintegration and dissolution tests. RESULTS: The granules formed hard tablets (tensile strength 1 - 2.0 ...

  12. 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.

  13. [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.

  14. 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.

  15. 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.

  16. 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.

  17. Sublingual injection of microparticles containing glycolipid ligands for NKT cells and subunit vaccines induces antibody responses in oral cavity.

    Science.gov (United States)

    DeLyria, Elizabeth S; Zhou, Dapeng; Lee, Jun Soo; Singh, Shailbala; Song, Wei; Li, Fenge; Sun, Qing; Lu, Hongzhou; Wu, Jinhui; Qiao, Qian; Hu, Yiqiao; Zhang, Guodong; Li, Chun; Sastry, K Jagannadha; Shen, Haifa

    2015-03-20

    Natural Killer T (NKT) cells are a unique type of innate immune cells which exert paradoxical roles in animal models through producing either Th1 or Th2 cytokines and activating dendritic cells. Alpha-galactosylceramide (αGalCer), a synthetic antigen for NKT cells, was found to be safe and immune stimulatory in cancer and hepatitis patients. We recently developed microparticle-formulated αGalCer, which is selectively presented by dendritic cells and macrophages, but not B cells, and thus can avoid the anergy of NKT cells. In this study, we have examined the immunogenicity of microparticles containing αGalCer and protein vaccine components through sublingual injection in mice. The results showed that sublingual injection of microparticles containing αGalCer and ovalbumin triggered IgG responses in serum (titer >1:100,000), which persisted for more than 3months. Microparticles containing ovalbumin alone also induced comparable level of IgG responses. However, immunoglobulin subclass analysis showed that sublingually injected microparticles containing αGalCer and ovalbumin induced 20 fold higher Th1 biased antibody (IgG2c) than microparticles containing OVA alone (1:20,000 as compared to 1:1000 titer). Sublingual injection of microparticles containing αGalCer and ovalbumin induced secretion of both IgG (titer >1:1000) and IgA (titer=1:80) in saliva secretion, while microparticles containing ovalbumin alone only induced secretion of IgG in saliva. Our results suggest that sublingual injection of microparticles and their subsequent trafficking to draining lymph nodes may induce adaptive immune responses in mucosal compartments. Ongoing studies are focused on the mechanism of antigen presentation and lymphocyte biology in the oral cavity, as well as the toxicity and efficacy of these candidate microparticles for future applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. The effect of pre-procedure sublingual nitroglycerin on radial artery diameter and Allen's test outcome - Relevance to transradial catheterization.

    Science.gov (United States)

    Chong, Aun-Yeong; Lo, Ted; George, Sudhakar; Ratib, Karim; Mamas, Mamas; Nolan, James

    2017-07-29

    The radial artery is increasingly used for cardiac procedures, but is a relatively small vessel that is prone to spasm when instrumented. Intra-arterial nitroglycerine has been shown to reduce radial spasm but first requires arterial access. We investigated the effect of pre-procedure sublingual nitroglycerin (NTG) on the diameter of the radial artery in a large cohort of patients. 305 subjects underwent ultrasound measurement of their radial and ulnar arteries in both arms before and after the administration of 800μg of sublingual NTG. The Allen's test was also performed in the subjects prior to and after NTG. Radial artery diameter in this Caucasian study group is larger than that reported for other populations. The administration of sublingual NTG significantly increased the size of the right radial artery from 2.88±0.36mm to 3.36±0.40mm in men and from 2.23±0.37 up to 2.74±0.36mm in women. There were also significant increases in left radial, right and left ulnar artery diameters in males and females with NTG. There was no significant effect of NTG on blood pressure. In all patients with an unfavourable Allen's test, retesting following sublingual NTG resulted in transition to a favourable Allen's. Caucasian populations have larger calibre radial arteries compared to other geographic areas. Sublingual NTG is effective at dilating the radial artery in both men and women. This may make radial artery puncture and cannulation less challenging and should be considered in all patients in the absence of contraindications. The results of Allen's testing are dynamic and its usefulness for screening prior to transradial access is undetermined. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. 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...

  20. 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

  1. Product development of pumpkin tablet

    Directory of Open Access Journals (Sweden)

    Kamgoed, T.

    2007-05-01

    Full Text Available The development of pumpkin tablet was studied and the drying conditions of pumpkin using a double drum dryer were optimized. The study factors were drying agents (maltodextrin D.E.13-16 andtapioca flour at different levels (3 and 5%, drying temperatures (130 and 140oC and drum dryer speeds (4 and 5 rpm. The results showed that the optimal conditions were using 3% maltodextrin D.E.13-16, dryingtemperature of 130oC and drum dryer speed of 4 rpm. The moisture, fat, bulk density, reducing sugars and granulometric retention of the obtained pumpkin powder were 3.39%, 1.42%, 1.004 g/ml, 12.63% and 0.67%, respectively and L*, a* and b* values were 73.85, -0.60 and 35.23, respectively. A study of suitable amount of icing sugar using different contents for tablet production (0, 10, 20, 30 and 40% was performedand showed that using 20% icing sugar was the most acceptable. The obtained pumpkin tablet was subjected to chemical, physical and microbiological analysis. The ash, moisture, protein, fat, fiber and carbohydratecontents were 1.87, 3.60, 3.34, 1.00, 2.26 and 87.99%, respectively. The reducing sugars and β-carotene contents were 5.44±0.61% and 3.79±0.57 mg/100g, respectively. The Aw, hardness and solubility were 0.56,3.25 kgf and 25.00 %, respectively. The L*, a* and b* values were 79.85, 0.28 and 23.64, respectively. The total microbial count and the yeast and mould count were <10 CFU/g. The shelf life of the pumpkin tabletwas at least 4 months at room temperature (35±2oC.

  2. 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...

  3. Tablet computers in the veterinary curriculum.

    Science.gov (United States)

    Eurell, Jo Ann C; Diamond, Nancy A; Buie, Brandon; Grant, David; Pijanowski, Gerald J

    2005-01-01

    Tablet computers offer a new method of information management in veterinary medical education. With the tablet computer, students can annotate class notes using electronic ink, search for keywords, and convert handwriting to text as needed. Additional electronic learning resources, such as medical dictionaries and electronic textbooks, can be readily available. Eleven first-year veterinary students purchased tablet computers and participated in an investigation of their working methods and perceptions of the tablet computer as an educational tool. Most students found the technology useful. The small size and portability of the tablet allowed easy transport and use in a variety of environments. Most students adapted to electronic notetaking by the second week of classes; negative experiences with the tablet centered on a failure to become comfortable with taking notes and navigating on the computer as opposed to writing and searching on paper. A few performance-related problems, including short battery life, were reported. Tablet software allowed conversion of faculty course notes from a variety of original formats, meaning that instructors could maintain their original methods of note preparation. Adopting a consistent naming convention for files helped students to locate the files on their computers, and smaller file sizes helped with computer performance. Collaboration between students was fostered by tablet use, which offers possibilities for future development of collaborative learning environments.

  4. 21 CFR 520.1510 - Nitenpyram tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Nitenpyram tablets. 520.1510 Section 520.1510 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... order of a licensed veterinarian. (d) Conditions of use—(1) Dogs—(i) Amount—(A) One 11.4-mg tablet for...

  5. 21 CFR 520.1900 - Primidone tablets.

    Science.gov (United States)

    2010-04-01

    ... for use of 50 and 250 milligram tablets. (c) Conditions of use in dogs—(1) Amount. Twenty-five... information. (2) Indications for use. For the control of convulsions associated with idiopathic epilepsy... recognizable lesion in certain entities in dogs.1 (3) Limitations. The tablets may be administered whole or...

  6. Quantitative Determination of Metformin Hydrochloride in Tablet ...

    African Journals Online (AJOL)

    Purpose: To develop and validate a suitable method for the assay of metformin hydrochloride (HCl) in tablets containing croscarmellose sodium as an additive. Methods: Methanol and ethanol (99%) were assessed as solvents for sample preparation for the assay of metformin HCl in tablets containing croscarmellose ...

  7. Tablet Keiti: Does it Contain Astronomical Instructions?

    DEFF Research Database (Denmark)

    Wieczorek, Rafal

    2010-01-01

    E – contains a pattern that can well be interpreted as another calendrical instruction, quite similar in nature to the Mamari calendar. Engraved on tablet Keiti is a string of glyphs known as sequence alpha 1-10, which is repeated 10 times throughout one side of the tablet. This repetitious string...

  8. Pharmacokinetic Studies on Metoprolol - Eudragit Matrix Tablets ...

    African Journals Online (AJOL)

    Purpose: To investigate the pharmacokinetics of of a developed metoprolol and a reference standard (Mepressor®). Methods: Metoprolol tartrate-loaded Eudragit® FS microparticles were formulated and compressed into tablets. The tablets were tested for their physicochemical properties according to United States ...

  9. Transforming the Classroom With Tablet Technology.

    Science.gov (United States)

    Sargent, Lana; Miles, Elizabeth

    Identifying the most effective models for integrating new technology into the classroom and understanding its effects on educational outcomes are essential for nurse educators. This article describes an educational intervention with tablet technology (iPads) using an innovative case-based learning model in a nursing program. Students reported positive learning outcomes when using the tablet technology for learning course content.

  10. Breaking of scored tablets : a review

    NARCIS (Netherlands)

    van Santen, E; Barends, D M; Frijlink, H W

    The literature was reviewed regarding advantages, problems and performance indicators of score lines. Scored tablets provide dose flexibility, ease of swallowing and may reduce the costs of medication. However, many patients are confronted with scored tablets that are broken unequally and with

  11. Development and characterization of orodispersible tablets of ...

    African Journals Online (AJOL)

    Purpose: The purpose of the present research was to the effect of camphor as a subliming agent on the mouth dissolving property of famotidine tablets. Method: Orodispersible tablets of famotidine were prepared using camphor as subliming agent and sodium starch glycollate together with crosscarmellose sodium as ...

  12. 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.

  13. Absorption of effervescent paracetamol tablets relative to ordinary paracetamol tablets in healthy volunteers.

    Science.gov (United States)

    Rygnestad, T; Zahlsen, K; Samdal, F A

    2000-05-01

    The aim of this study was to compare the rate of absorption between ordinary paracetamol tablets and effervescent paracetamol tablets. Twenty healthy volunteers participated in an open randomised crossover study and were given a 1000-mg dose of either ordinary paracetamol tablets (2 x 500 mg Panodil tablets, SmithKline Beecham) or effervescent paracetamol tablets (2 x 500 mg Pinex Brusetablett, Alpharma AS) with a 3-week washout period in between. Blood samples were collected for 3 h. Maximum serum concentration (Cmax) and the time to maximum serum concentration (tmax) were recorded and the area under the concentration versus time curve (AUC) was calculated. The mean tmax was significantly shorter when paracetamol effervescent tablets were taken (27 min) rather than ordinary paracetamol tablets (45 min) (P = 0.004). There was no significant difference between the mean Cmax of 143 micromol/l with effervescent tablets and that of 131 micromol/l with ordinary tablets. The mean AUC(0-3 h) was significantly higher with paracetamol effervescent tablets (223.8 micromol x h x l(-1)) than with ordinary tablets (198.2 micromol x h x l(-1); P = 0.003). After 15 min, 17 (85%) subjects in the effervescent group had a serum concentration of 70 micromol/l (lower therapeutic serum concentration) or higher relative to only 2 (10%) subjects in the ordinary tablet group (P = 0.001). Paracetamol effervescent tablets are absorbed significantly faster than ordinary paracetamol. Thus, effervescent tablets might offer significantly faster pain relief when paracetamol is used.

  14. 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

  15. Tablet--next generation sequence assembly visualization.

    Science.gov (United States)

    Milne, Iain; Bayer, Micha; Cardle, Linda; Shaw, Paul; Stephen, Gordon; Wright, Frank; Marshall, David

    2010-02-01

    Tablet is a lightweight, high-performance graphical viewer for next-generation sequence assemblies and alignments. Supporting a range of input assembly formats, Tablet provides high-quality visualizations showing data in packed or stacked views, allowing instant access and navigation to any region of interest, and whole contig overviews and data summaries. Tablet is both multi-core aware and memory efficient, allowing it to handle assemblies containing millions of reads, even on a 32-bit desktop machine. Tablet is freely available for Microsoft Windows, Apple Mac OS X, Linux and Solaris. Fully bundled installers can be downloaded from http://bioinf.scri.ac.uk/tablet in 32- and 64-bit versions.

  16. Sublingual tacrolimus administration provides similar drug exposure to per-oral route employing lower doses in liver transplantation: a pilot study.

    Science.gov (United States)

    Solari, S; Cancino, A; Wolff, R; Norero, B; Vargas, J I; Barrera, F; Guerra, J F; Martínez, J; Jarufe, N; Soza, A; Arrese, M; Benitez, C

    2017-05-01

    Per-oral tacrolimus administration is not always practicable. Sublingual administration is a potential alternative, but its feasibility and effectiveness compared with oral route has not been established. To compare tacrolimus drug exposure after sublingual and oral administration in liver transplant recipients. Experimental, open-label, non-randomised, cross-over study. Tacrolimus exposure was evaluated in 32 liver transplant recipients receiving oral administration. 12 h tacrolimus area-under-the-curve (AUC0-12 h ) was calculated using tacrolimus blood concentrations at 0-0.5-1-2-4-6-8-12 hrs post-dose. Recipients were switched to sublingual administration, and dose was adjusted to reach similar trough levels, new AUC0-12 h was calculated. Correlation between AUC0-12 h and trough levels was determined for both oral and sublingual phases. Similar trough levels were accomplished with oral and sublingual administration (6.68 ± 2 ng/mL vs. 6.62 ± 1.9 ng/mL (P = 0.8)). Although concentration 2 h post dose was higher in oral phase (15.36 ± 7.14 vs. 13.18 ± 5.64, P = 0.015), AUC0-12 h was similar in both phases (116.6 ± 34.6 vs. 111.5 ± 36.93 ng/mL* h, P = 0.19). Daily dose of tacrolimus required in sublingual phase was 37% lower than that used in oral phase (P tacrolimus when employing sublingual route. Good correlation between AUC0-12 h and trough levels was observed in sublingual phase (r2 = 0.74). Twenty-two recipients were maintained on sublingual administration after the end of study (mean follow-up: 18.7 ± 5.8 months). No difference in liver function tests or rejection rates was found during follow-up period. Sublingual administration of tacrolimus is feasible and provides similar drug exposure compared with oral administration. In our study, at long-term follow-up, sublingual administration was not associated with liver transplant rejection. © 2017 John Wiley & Sons Ltd.

  17. Mathematical tablets from Tell Harmal

    CERN Document Server

    Gonçalves, Carlos

    2015-01-01

    This work offers a re-edition of twelve mathematical tablets from the site of Tell Harmal, in the borders of present-day Baghdad. In ancient times, Tell Harmal was Šaduppûm, a city representative of the region of the Diyala river and of the kingdom of Ešnunna, to which it belonged for a time. These twelve tablets were originally published in separate articles in the beginning of the 1950s and mostly contain solved problem texts. Some of the problems deal with abstract matters such as triangles and rectangles with no reference to daily life, while others are stated in explicitly empirical contexts, such as the transportation of a load of bricks, the size of a vessel, the number of men needed to build a wall and the acquisition of oil and lard. This new edition of the texts is the first to group them, and takes into account all the recent developments of the research in the history of Mesopotamian mathematics. Its introductory chapters are directed to readers interested in an overview of the mathematical con...

  18. 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

  19. Influence of sublingual captopril on plasma catecholamine levels during hypertensive emergencies and cold immersion.

    Science.gov (United States)

    Polonia, J J; Monteiro, A; Esteves, A; Cunha, M E; Santos, M L; Coutinho, J; Coelho, J L; Brandao, F A; Cerqueira-Gomes, M

    1988-03-11

    Experimental evidence of captopril-induced inhibition of sympathetic activity, mediated by decrease in angiotensin II production, is presented. The blood pressure, plasma catecholamine, plasma renin activity, and plasma aldosterone responses to a single dose of sublingual captopril in 23 patients with hypertensive emergencies were evaluated. The major correlation found was between the captopril-induced decrease in blood pressure and the decrease in plasma norepinephrine levels (r = 0.57, p less than 0.01). In another 11 hypertensive patients with normal or high renin levels, captopril lowered by 65 percent the increase in plasma norepinephrine induced by cold immersion of the forearm. In both circumstances, plasma renin and aldosterone levels changed in accordance with the expected inhibition of angiotensin converting enzyme activity. These data suggest that, in selected circumstances in hypertensive patients, captopril exhibits a depressive influence on sympathetic activity along with the inhibition of the renin-angiotensin system.

  20. Fentanyl sublingual spray for breakthrough cancer pain in patients receiving transdermal fentanyl.

    Science.gov (United States)

    Alberts, David S; Smith, Christina Cognata; Parikh, Neha; Rauck, Richard L

    2016-10-01

    To investigate the relationship between effective fentanyl sublingual spray (FSS) doses for breakthrough cancer pain (BTCP) and around-the-clock (ATC) transdermal fentanyl patch (TFP). Adults tolerating ATC opioids received open-label FSS for 26 days, followed by a 26-day double-blind phase for patients achieving an effective dose (100-1600 µg). Out of 50 patients on ATC TFP at baseline, 32 (64%) achieved an effective dose. FSS effective dose moderately correlated with mean TFP dose (r = 0.4; p = 0.03). Patient satisfaction increased during the study. Common adverse event included nausea (9%) and peripheral edema (9%). FSS can be safely titrated to an effective dose for BTCP in patients receiving ATC TFP as chronic cancer pain medication. ClinicalTrials.gov identifier: NCT00538850.

  1. Effect of vasopressin on sublingual microcirculation in a patient with distributive shock.

    Science.gov (United States)

    Dubois, Marc J; De Backer, Daniel; Creteur, Jacques; Anane, Sami; Vincent, Jean-Louis

    2003-06-01

    To assess the sublingual microcirculation in a patient during vasopressin administration for a distributive shock after cardiopulmonary bypass. Case-report in the Department of Intensive Care of a university hospital. A 53 year-old man developed severe distributive shock after cardiac transplant, requiring massive doses of vasopressor agents. Vasopressin administered twice at a dose of 0.02 U/min increased mean blood pressure and allowed partial weaning of other vasopressor drugs. Microcirculatory alterations were assessed by orthogonal polarization spectral technique: 50% and 60% of capillaries were perfused at baseline, and these proportions did not worsen when vasopressin was administered. Despite its strong vasopressor effects vasopressin infusion did not worsen microcirculatory alterations in this patient with distributive shock following cardiac surgery.

  2. A Case of Sublingual Dermoid Cyst: Extending the Limits of the Oral Approach

    Directory of Open Access Journals (Sweden)

    Nobuo Ohta

    2012-01-01

    Full Text Available We present the case of a dermoid cyst with an oral and a submental component in a 21-year-old Japanese woman who presented with complaints of a mass in the oral cavity and difficulty in chewing and swallowing solid foods for about 2 years. MRI shows a 55 × 65 mm well-circumscribed cystic mass extending from the sublingual area to the mylohyoid muscle. Under general anesthesia and with nasotracheal intubation, the patient underwent surgical removal of the mass. Although the cyst was large and extending mylohyoid muscle, intraoral midline incision was performed through the mucosa overlying the swelling and the cyst was separated from the surrounding tissues with appropriate traction and countertraction and successfully removed without extraoral incision. Oral approach in surgical enucleation is useful procedure to avoid cosmetic problems in large and extending mylohyoid muscle cyst.

  3. Comparison between effects of intravenous lidocaine and sublingual nifedipine on preventing blood pressure increase in laryngoscopy

    Directory of Open Access Journals (Sweden)

    Gholamreza Mohseni

    2010-06-01

    Full Text Available Gholamreza Mohseni1, Azam Kolyaei2, Morteza Farshchian3, Mansour Rezaei4, Negin Ghadami51Anesthesiologist, assistant professor, 2Anesthetist, 3Orthopedist, assistant professor, 4Biostatistician, assistant professor, 5General practitioner, Kermanshah University of Medical Sciences, Kermanshah, IranIntroduction: Arrhythmia during surgery most frequently occurs during laryngoscopy and intratracheal intubation. Many surgical procedures require intratracheal intubation, which results in hemodynamic changes. These changes in ill patients and patients with limited coronary flow reserve are associated with serious events.Materials and methods: A randomized clinical trial was performed on 124 healthy patients who were elective surgery candidates at Taleghani hospital in Kermanshah. Patients were allocated randomly to each equal group of 62 patients with 95% significance and 90% power of test-retest for sample size. The patients had no history of disease or use of special medications. Drugs commonly used for laryngoscopy and intubation to prevent hemodynamic complications, intravenous lidocaine and sublingual nifedipine, were compared with independent and paired t-tests.Results: This comparison suggested that while the mean age, weight, and sex distribution in our two groups were the same, mean changes in systolic and diastolic blood pressure and heart rate increases in the lidocaine group were 12.6%, 7.5%, and 16.5%, and in the nifedipine group, 17.7%, 11.0%, and 23.5% (P value = 0.0052, 0.189, and 0.0001, respectively. Conclusion: According to the results of our study, intravenous lidocaine is more effective than sublingual nifedipine for preventing hemodynamic changes while performing laryngoscopy or intratracheal intubation.Keywords: hemodynamic changes, laryngoscopy

  4. Uso y abuso del nifedipino por vía sublingual en nuestros sistemas de urgencia

    Directory of Open Access Journals (Sweden)

    Nancy Guinart Zayas

    1998-04-01

    Full Text Available Se observa que el incremento de la prevalencia de pacientes hipertensos en nuestras comunidades, y la implantación del Programa Nacional para el control de la hipertensión arterial, no han podido disminuir la cantidad de pacientes que acuden con cifras altas de su presión arterial a nuestros servicios de urgencia con decisiones terapéuticas indiscriminadas y agresivas. Se ha generalizado el uso del nifedipino sublingual, incluso en pacientes de la tercera edad, lo que produce bajadas bruscas de la presión arterial por disminución en la sensibilidad de los barorreceptores y con ellas una alteración de los mecanismos de autorregulación del flujo hístico. Se señala que las complicaciones producidas no son alarmantes, pero con un uso racional y si se cumplen algunas normas, podrían disminuirse aún másIt is observed that the prevalence increase of hypertensive patients in our communities and the implementation of the National Program for the Hypertension Control have not so far been able to reduce the number of hypertensive patients going to our emergency medical services by applying indiscriminate and aggressive therapeutical methods. The use of sublingual administered nifedipine is extensive even in elderly patients, which may cause a sharp blood pressure drop and also a change in the hystic flow self-regulating mechanisms. It is stressed that complications are not serious but if this drug is more rationally used and some directions are fulfilled, then these complications will be further reduced

  5. COMPARISON OF SUBLINGUAL THERAPEUTIC VACCINE WITH ANTIBIOTICS FOR THE PROPHYLAXIS OF RECURRENT URINARY TRACT INFECTIONS

    Directory of Open Access Journals (Sweden)

    María Fernanda Lorenzo-Gómez

    2015-06-01

    Full Text Available Objective: To evaluate the clinical impact of the prophylactic treatment with sublingual immunostimulation in the prevention of recurrent urinary tract infections (rUTIs compared with the use of antibiotics.Material and Methods: Retrospective cohort study evaluating the clinical records of 669 women with rUTIs; 339 had a 6-month prophylaxis with antibiotics and 360 had a 3-month prophylaxis with a sublingual bacterial preparation (MV 140-Uromune®. The time after the prophylaxis-period until the appearance of a new infection (assessed by uroculture was scored during one year. Absolute risk reduction (ARR and number needed to treat (NNT were also calculated.Results: All patients (100% treated with antibiotics experienced a new UTI during the scoring period of 12 months, being the mean time free of UTI 29 (±38 days. In the group treated with the bacterial preparation, only 35 (9.7% patients experienced UTI in the same period. Kaplan-Meier curves comparing the accumulated survival (disease-free time between both groups were significant (P < 0.0001. ARR was 90.28 % (87.18-93.38 and NNT 1.1 (1.1-1.1.Conclusions: These results suggest that the treatment with the bacterial preparation reduces rUTIs very effectively, arising as an effective strategy to reduce the frequency of rUTIs. It reduces antibiotic consumption, matching the current recommendations due to the raise of antimicrobial resistance. Randomized, double-blind and placebo-controlled, clinical trials are needed to establish more accurately the clinical impact of this bacterial preparation in patients with rUTIs.

  6. [Failure of sublingual immunotherapy to treat latex allergy. A report of a case].

    Science.gov (United States)

    Morfin Maciel, Blanca María; Castillo Morfin, Blanca María

    2008-01-01

    Natural rubber latex has been in widespread use for over a century. Reports of immediate hypersensitivity to latex have increased dramatically since the first case was reported in 1979, specially in persons with cumulative latex exposure. A 13 year old male was referred to our office. He had been wearing orthodontic rubber bands for two years. The previous year he started having itchy, red and watery eyes, with sneezing and runny nose when he was exposed to rubber products. Then he developed oral edema and lip ulcers. Finally, he experienced cough, wheezing, chest tightness and dyspnea. The patient had no history of undergoing surgery, and his mother denied pacifier use. He had no history of fruit and vegetables allergy. Physical examination revealed conjunctival hyperemia, with fine papillary response in the upper tarsal plate, hyaline rhinorrhea, turbinate hypertrophy and perioral ulcers. Skin prick test were positive for latex and Quercus albus. Patch test with latex glove was negative, but positive with rubber tourniquet. Total IgE was 365 UI/mL. Latex-specific IgE testing confirmed the diagnosis. Spirometric values were normal. He started rush sublingual immunotherapy with latex extract. When he had finished, he traveled abroad. At immigration the inspectors examined him with latex gloves. Immediately he developed anaphylaxis, needing urgent medical attention. Although the efficacy and safety of sublingual immunotherapy for latex allergy has been demonstrated, the most effective strategy is complete avoidance of latex-containing products. World Public Health Services must promote the use of synthetic elastomer gloves in airports worldwide.

  7. Sublingual Immunotherapy Induces Regulatory Function of IL-10-Expressing CD4+CD25+Foxp3+ T Cells of Cervical Lymph Nodes in Murine Allergic Rhinitis Model

    Directory of Open Access Journals (Sweden)

    Takaya Yamada

    2012-01-01

    Full Text Available Sublingual immunotherapy (SLIT has been considered to be a painless and efficacious therapeutic treatment of allergic rhinitis which is known as type I allergy of nasal mucosa. Nevertheless, its mechanisms need to be further investigated. In this study, we constructed an effective murine model of sublingual immunotherapy in allergic rhinitis, in which mice were sublingually administered with ovalbumin (OVA followed by intraperitoneal sensitization and nasal challenge of OVA. Sublingually treated mice showed significantly decreased specific IgE responses as well as suppressed Th2 immune responses. Sublingual administration of OVA did not alter the frequency of CD4+CD25+ regulatory T cells (Tregs, but led to upregulation of Foxp3- and IL-10-specific mRNAs in the Tregs of cervical lymph nodes (CLN, which strongly suppressed Th2 cytokine production from CD4+CD25− effector T cells in vitro. Furthermore, sublingual administration of plasmids encoding the lymphoid chemokines CCL19 and CCL21-Ser DNA together with OVA suppressed allergic responses. These results suggest that IL-10-expressing CD4+CD25+Foxp3+ Tregs in CLN are involved in the suppression of allergic responses and that CCL19/CCL21 may contribute to it in mice that received SLIT.

  8. Phase transformation in thiamine hydrochloride tablets: Influence on tablet microstructure, physical properties, and performance.

    Science.gov (United States)

    Chakravarty, Paroma; Suryanarayanan, Raj; Govindarajan, Ramprakash

    2012-04-01

    The objective of this article was to monitor phase transformation in thiamine hydrochloride, from a nonstoichiometric hydrate (NSH) to a hemihydrate (HH), in stored tablets, prepared both by direct compression and wet granulation, and to relate the storage-induced phase transformation with changes in tablet microstructure, physical properties, and performance. Raman spectroscopy revealed complete NSH → HH transformation in tablets, within 30 h of storage at 40°C/75% relative humidity. When the tablets were prepared by wet granulation of NSH alone, there was a marked increase in both tablet volume and hardness on storage. However, when microcrystalline cellulose (MCC) was included in granulation, the resulting stored tablets also exhibited a pronounced increase in disintegration time. In contrast, tablets prepared by dry processing via compression of a NSH-MCC physical mixture did not exhibit any changes in properties, despite the in situ solid form conversion. Scanning electron microscopy revealed growth of needle-like HH crystals in all stored tablets and mercury porosimetry revealed considerable changes in the pore size distribution during storage. Longer storage led to crystal growth (Ostwald ripening), causing further gradual but less dramatic changes in properties. The phase transformation and the complex interparticulate associations in the tablet influenced the changes in tablet microstructure, compact physical properties, and product behavior. Copyright © 2011 Wiley Periodicals, Inc.

  9. Nitroglycerin Sublingual

    Science.gov (United States)

    ... ergotamine (in Cafergot, in Migergot), and methylergonovine (Methergine) heparin; medications for high blood pressure, heart failure, or ... such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant ...

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

    Directory of Open Access Journals (Sweden)

    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.

  11. The tabletting properties of Stearolac-S | Onyechi | Journal of ...

    African Journals Online (AJOL)

    The effects of the excipients on tablet hardness, friability, disintegration and dissolution rate were also evaluated. Tablets containing 3 - 4 % w/w STEAROLAC-S gave unit ejection force values comparable to those of tablets containing 2% w/w magnesium stearate. Tablets containing 4% STEAROLAC-S exhibited better ...

  12. 21 CFR 520.82a - Aminopropazine fumarate tablets.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Aminopropazine fumarate tablets. 520.82a Section... Aminopropazine fumarate tablets. (a) Specifications. The drug is in tablet form. Each tablet contains aminopropazine fumarate equivalent to 25 milligrams of aminopropazine base. (b) Sponsor. See No. 000061 in § 510...

  13. 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.

  14. Teach yourself visually Windows 8 tablets

    CERN Document Server

    McFedries, Paul

    2012-01-01

    A visual guide to all the features of the new Windows 8 Tablet This must-have resource features visually rich, step-by-step instructions that show you how to get the most enjoyment from your Windows 8 tablet. Learn about the exciting new Metro UI, optimized specifically for touch devices. The most popular and commonly used apps and functions are covered too, along with the basics of syncing with a network, setting up e-mail, watching videos, listening to music, and common productivity tasks. This book provides all the guidance needed to enjoy all the best the new Windows 8 tablets have to offe

  15. Android Tablet Application Development For Dummies

    CERN Document Server

    Felker, Donn

    2011-01-01

    Get up to speed on the hottest opportunity in the application development arena App development for tablets is a booming business. Android tablets, including the popular Motorola Xoom, are gaining market share at breakneck speed, and this book can have even novice programmers creating great Android apps specifically for tablets quickly and easily. A little Java knowledge is helpful but not essential to get started creating apps. Android expert Donn Felker helps you get the Android environment up and running, use XML to create application menus, create an icon for your app, and submit your app

  16. Tablets for Learning in Higher Education

    DEFF Research Database (Denmark)

    Godsk, Mikkel

    are related to its ability to support engaging, inclusive, and/or collaborative learning, to provide flexibility in place, and to include multimedia and interactive content in teaching practice. However, performing the review also revealed that the notion of tablets for learning is equivocal. As a consequence......Based on a small-scale literature review this paper identifies the top 10 affordances of post PC tablets (sometimes referred to as ‘tablet computers’) for higher education in settings where the technology is used for learning. The review shows that the predominant affordances of the technology...

  17. Dissolution test for glibenclamide tablets

    Directory of Open Access Journals (Sweden)

    Elisabeth Aparecida dos Santos Gianotto

    2007-10-01

    Full Text Available The aim of this work is to develop and validate a dissolution test for glibenclamide tablets. Optimal conditions to carry out the dissolution test are 500 mL of phosphate buffer at pH 8.0, paddles at 75 rpm stirring speed, time test set to 60 min and using equipment with six vessels. The derivative UV spectrophotometric method for determination of glibenclamide released was developed, validated and compared with the HPLC method. The UVDS method presents linearity (r² = 0.9999 in the concentration range of 5-14 µg/mL. Precision and recoveries were 0.42% and 100.25%, respectively. The method was applied to three products commercially available on the Brazilian market.

  18. 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

  19. 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

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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.

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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