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Sample records for fluvoxamine extended release

  1. Sulpiride in combination with fluvoxamine increases in vivo dopamine release selectively in rat prefrontal cortex.

    Science.gov (United States)

    Ago, Yukio; Nakamura, Shigeo; Baba, Akemichi; Matsuda, Toshio

    2005-01-01

    Coadministration of atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs) enhances the release of monoamines such as dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the prefrontal cortex. To clarify the role of DA-D2/3 receptors in the combination effect, we examined the effects of coadministration of the selective DA-D2/3 antagonist sulpiride and the SSRI fluvoxamine on amine neurotransmitter release in rat prefrontal cortex. Sulpiride (10 mg/kg, i.p.) and fluvoxamine (10 mg/kg, i.p.) alone did not affect extracellular DA levels, while their coadministration caused a significant increase in DA levels. Sulpiride alone did not affect extracellular levels of 5-HT and NE in the prefrontal cortex, while fluvoxamine alone caused a marked increase in 5-HT levels and a slight increase in NE levels. Sulpiride did not affect the fluvoxamine-induced increases in extracellular levels of 5-HT and NE. The DA-D2/3 antagonist haloperidol (0.1 mg/kg) in combination with fluvoxamine also caused a selective increase in extracellular DA levels in the cortex. Coadministration of sulpiride and fluvoxamine did not affect extracellular DA levels in the striatum. Combination of systemic sulpiride and local fluvoxamine did not increase the DA levels, but that of systemic fluvoxamine with local sulpiride increased. The combination effect in increasing prefrontal DA levels was antagonized systemically, but not locally, by the 5-HT1A antagonist WAY100635 at a low dose. These findings suggest that the combination of prefrontal DA-D2/3 receptor blockade and 5-HT1A receptor activation in regions other than the cortex plays an important role in sulpiride and fluvoxamine-induced increase in prefrontal DA release.

  2. Controlled-release fluvoxamine in obsessive-compulsive disorder and social phobia.

    Science.gov (United States)

    Owen, Richard T

    2008-12-01

    Specific serotonin reuptake inhibitors are currently recommended as first-line treatments for obsessive-compulsive disorder (OCD) and social phobia or social anxiety disorder (SAD). Fluvoxamine has demonstrated efficacy in both these conditions and has recently been marketed in a controlled-release (CR) formulation in the United States for treatement of OCD and SAD. Three 12-week double-blind, multicenter, randomized, placebo-controlled studies were conducted with this formulation - two in SAD and one in OCD. All three studies showed a robust effect on the key symptoms of OCD and SAD and had broadly comparable efficacy to studies conducted with immediate-release (IR) fluvoxamine. The beneficial effects of fluvoxamine CR were maintained in a 12-week double-blind, randomized extension to one SAD trial. The CR formulation, when compared to its IR counterpart, offers less daily fluctuation in fluvoxamine levels and a more rapid titration schedule; in addition, a more rapid onset of effect may result from these features. Overall, the benefits of the CR formulation, among them the convenience of oncedaily dosing, were achieved without an increased adverse event burden versus the IR form.

  3. Aggravation of glaucoma with fluvoxamine.

    Science.gov (United States)

    Jiménez-Jiménez, F J; Ortí-Pareja, M; Zurdo, J M

    2001-12-01

    To report a case of aggravation of glaucoma associated with the use of fluvoxamine. A 66-year-old while woman diagnosed with narrow-angle glaucoma showed an increase in intraocular pressure and experienced orbital pain and blurred vision after the initiation of fluvoxamine for tension-type headache. These symptoms disappeared and intraocular pressure normalized after withdrawal of this drug. Aggravation of narrow-angle glaucoma is a well-known adverse effect of tricyclic antidepressants. Because this adverse effect had been rarely reported to date with selective serotonin-reuptake inhibitors (paroxetine and fluoxetine), we used fluvoxamine in our patient. The disappearance of ocular symptoms and the normalization of intraocular pressure two days after stopping fluvoxamine suggest a possible relationship between fluvoxamine and aggravation of glaucoma. Fluvoxamine should be considered as a drug that can induce or aggravate narrow-angle glaucoma.

  4. Antidepressant-like effect of coadministration of sulpiride and fluvoxamine in mice.

    Science.gov (United States)

    Ago, Yukio; Harasawa, Toshiya; Itoh, Soichi; Nakamura, Shigeo; Baba, Akemichi; Matsuda, Toshio

    2005-09-27

    We have recently reported that coadministration of sulpiride, an antipsychotic drug, and fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor, selectively increases in vivo dopamine release in the prefrontal cortex. This study examined the effects of coadministration of these drugs on duration of immobility in the tail suspension test using mice. Neither sulpiride (3 or 10 mg/kg) nor fluvoxamine (10 or 20 mg/kg) alone affected immobility time, whereas coadministration significantly reduced immobility time. WAY 100635, a 5-HT(1A) receptor antagonist, did not affect the effects of sulpiride and fluvoxamine coadministration, but reduced immobility time in combination with fluvoxamine (20 mg/kg). A high dose of fluvoxamine alone (60 mg/kg) also reduced immobility time. These results suggest that the antidepressant-like effects of fluvoxamine in combination with sulpiride or WAY 100635 in the tail suspension test are mediated by the activation of dopamine or 5-HT systems, respectively.

  5. Electroanalytical study of fluvoxamine.

    Science.gov (United States)

    Nouws, Henri P A; Delerue-Matos, Cristina; Barros, Aquiles A; Rodrigues, José A; Santos-Silva, Alice

    2005-08-01

    Fluvoxamine (FVX) can be reduced at a mercury-drop electrode, with a maximum peak current intensity being obtained at a potential of -0.7 V vs. Ag/AgCl, in an aqueous electrolyte solution of pH 2. The compound was determined in a pharmaceutical product and in spiked human serum by square-wave adsorptive-stripping voltammetry (SWAdSV) after accumulation at the electrode surface, under batch conditions. Because the presence of dissolved oxygen did not interfere significantly with the analysis, it was also possible to determine FVX in the pharmaceutical product by use of a flow-injection analysis (FIA) system with SWAdSV detection. The methods developed were validated and successfully applied to the quantification of FVX in a pharmaceutical product. Recoveries between 76 and 89% were obtained in serum analysis. The FIA-SWAdSV method enabled analysis of up to 120 samples per hour at reduced cost, implying the possibility of competing with the chromatographic methods usually used for this analysis.

  6. Pramipexole extended release: in Parkinson's disease.

    Science.gov (United States)

    Chwieduk, Claudine M; Curran, Monique P

    2010-04-01

    Pramipexole extended release (ER) is a non-ergolinic dopamine receptor agonist available for use as a once-daily oral treatment for the signs and symptoms of early and advanced idiopathic Parkinson's disease. Once-daily pramipexole ER and three times-daily pramipexole immediate release (IR) have similar exposure over 24 hours. The ER formulation is associated with fewer fluctuations in plasma pramipexole concentrations over this period. Pramipexole ER improved the symptoms of Parkinson's disease in three well designed trials in adults with early or advanced disease, as measured by changes from baseline in the sum of the Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III subtotal scores. In a 9-week study, the majority of patients with early Parkinson's disease who were receiving stable pramipexole IR treatment were successfully switched to pramipexole ER. Relative to placebo at week 18, pramipexole ER 0.375-4.5 mg (of the salt) once daily significantly decreased the sum of the UPDRS parts II and III subtotal scores from baseline in two trials in patients with early or advanced Parkinson's disease, and also reduced the percentage of off-time during waking hours in patients with advanced disease. The efficacy of pramipexole ER was maintained after 33 weeks of treatment in the trials in patients with early or advanced Parkinson's disease. Pramipexole ER was generally well tolerated in patients with Parkinson's disease, with the rate of adverse events being generally similar to that with pramipexole IR.

  7. Pramipexole extended release in Parkinson's disease.

    Science.gov (United States)

    Hametner, Eva-Maria; Seppi, Klaus; Poewe, Werner

    2011-09-01

    Pramipexole extended release (ER) is a new once-daily formulation of pramipexole, a nonergot dopamine agonist, which is available in five dosage strengths: 0.26 (0.375) mg, 0.52 (0.75) mg, 1.05 (1.5) mg, 2.1 (3) mg and 3.15 (4.5) mg (all doses are expressed in terms of pramipexole base and the corresponding dose strengths of pramipexole salt are given in brackets). Pramipexole ER is currently approved as monotherapy in early Parkinson's disease (PD), as well as an adjunct therapy to levodopa in advanced PD. Compared with the immediate release (IR) formulation, the ER formulation offers several advantages, including the potential for improved compliance owing to its simple once-daily dosing regimen and steadier plasma levels over 24 h. Double-blind, randomized, placebo and active comparator controlled trials in early, as well as advanced PD, established the superiority of both pramipexole ER and IR over placebo. The overnight switch from pramipexole IR three times a day to ER once-daily in early PD has been shown to be successful in more than 80% of patients. Pramipexole ER is well tolerated, with a similar adverse event profile to pramipexole IR. The aim of this article is to provide a short review of the most relevant pharmacological and clinical data on pramipexole ER.

  8. Liposomal extended-release bupivacaine for postsurgical analgesia

    National Research Council Canada - National Science Library

    Lambrechts, Mark; O'Brien, Michael J; Savoie, Felix H; You, Zongbing

    2013-01-01

    ..., inguinal hernia repair, total knee arthroplasty, and augmentation mammoplasty. However, like other bupivacaine formulations, the liposomal extended-release bupivacaine does have some side effects...

  9. Design and evaluation of nicorandil extended-release tablet

    Directory of Open Access Journals (Sweden)

    Ju-Young Kim

    2015-04-01

    Full Text Available The aim of this study was to design and evaluate extended-release formulations of a model drug, nicorandil, in order to achieve the desired steady-state plasma concentration of drug in vivo. Simulation was employed to estimate optimum dissolution and absorption rate of nicorandil. The dissolution test was employed using pH 1.2, 4.0, 6.8 buffer solution, or water, to measure the in vitro release behaviors of nicorandil formulations. A single dose (15 mg of each formulation was orally administered to four beagle dogs under fasted conditions, and the pharmacokinetic parameters were calculated. The in vitro/in vivo relationship of the extended-release formulation was confirmed using in vitro dissolution profiles and plasma concentrations of drug in beagle dogs. Nicorandil was released completely within 30 min from the immediate-release tablets and released for 24 h from the extended-release tablets. The nicorandil plasma concentration could be modified by adjusting the drug release rate from the extended-release formulation. The release rate of nicorandil was the rate-limiting step in the overall absorption of drug from the extended-release formulations. These results highlight the potential of a nicorandil extended-release formulation in the treatment of angina pectoris.

  10. Pramipexole Extended Release: A Novel Treatment Option in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Wolfram Eisenreich

    2010-01-01

    Full Text Available Pramipexole, the most commonly prescribed dopamine agonist worldwide, meanwhile serves as a reference substance for evaluation of new drugs. Based on numerous clinical data and vast experiences, efficacy and safety profiles of this non-ergoline dopamine agonist are well characterized. Since October 2009, an extended-release formulation of pramipexole has been available for symptomatic treatment of Parkinson's disease. Pramipexole administration can be cut down from three times to once a day due to the newly developed extended-release formulation. This is considerable progress in regard to minimizing pill burden and enhancing compliance. Moreover, the 24 h continuous drug release of the once-daily extended-release formulation results in fewer fluctuations in plasma concentrations over time compared to immediate-release pramipexole, given three times daily. The present study summarizes pharmacokinetics and all essential pharmacological and clinical characteristics of the extended-release formulation. In addition, it provides all study data, available so far, with regard to transition and de-novo administration of extended-release formulation for patients with Parkinson's disease. It further compares efficacy and safety data of immediate-release pramipexole with the extended-release formulation of pramipexole.

  11. Effect of different polymers on release of ranolazine from extended release tablets

    OpenAIRE

    Murthy, T. E. G. K.; Bhukya Swapna

    2013-01-01

    An extended release tablet provides prolonged release of drug, maintains the desired concentration of drug in plasma and thereby reduce dosing frequency, improve patient compliance and reduce the dose-related side-effects. Ranolazine is indicated for the chronic treatment of angina in patients who have not achieved an adequate response with other anti-anginal agent. The present investigation was undertaken to design the extended release tablets of ranolazine employing different polymers as ma...

  12. Metformin extended release: metformin gastric retention, metformin GR, metformin XR.

    Science.gov (United States)

    2005-01-01

    Metformin extended release [Glumetza, metformin hydrochloride, metformin gastric retention, metformin GR] is a proprietary once-a-day formulation of metformin hydrochloride under development with Depomed for the treatment of diabetes mellitus. In May 2002, Depomed licensed manufacturing and marketing rights for its proprietary formulation of metformin extended release (500mg dose) to Biovail Corporation for the US (including Puerto Rico) and Canada. Under the terms of the agreement, Biovail will pay DepoMed a 25 million dollars milestone fee upon approval of the 500mg dosage and also customary royalties on the net sales in the US and Canada. Biovail also agreed to acquire approximately 2.4 million of additionally issued Depomed shares for 12.3 million dollars. Biovail has subsequently developed a 1000mg dose of metformin extended release [metformin XR] using its proprietary Smartcoat delivery technology allowing a graduated release of the active drug from the tablet. In April 2004, Depomed and Biovail amended their original license agreement of May 2002. Under the terms of the amended agreement, Depomed will receive royalties on sales of Biovail's 1000mg tablet in the US and Canada. In turn, Biovail acquired access to Depomed's clinical data for the metformin 500mg tablet that will be used to accelerate regulatory filings for Biovail's 1000mg tablet and establish equivalence between the two dosages. Biovail is seeking marketing partners for metformin extended release (Glumetza) in the US. The company anticipates signing an agreement for the US during the second half of 2005. In Canada, Biovail Corporation will market Glumetzatrade mark through its Canadian division, Bioval Pharmaceuticals Canada. Depomed has an agreement with LG Life Sciences for the commercialisation and distribution of metformin extended release in Korea. Metformin GR is available for partnership in Europe and Asia. Biovail Corporation and Depomed announced in June 2005 that the US FDA has

  13. Fluvoxamine

    Science.gov (United States)

    ... over and over) and social anxiety disorder (extreme fear of interacting with others or performing in front ... memory problems, or confusion dry mouth headache nausea vomiting diarrhea stomach pain constipation indigestion gas change in ...

  14. Formulation and Evaluation of Darifenacin Hydrobromide Extended Release Matrix Tablets

    Directory of Open Access Journals (Sweden)

    Syed Meraj Sultana

    2016-08-01

    Full Text Available Darifenacin hydrobromide is a highly selective muscarinic (M3 receptor blocker that has been widely used for the treatment of overactive bladder syndrome. The bioavailability of darifenacin hydrobromide is 15–19% due to extensive first pass metabolism. Hence oral administration of darifenacin hydrobromide as extended tablets is a possible solution to overcome this problem. So the aim of the study was to formulate and evaluate Darifenacin hydrobromide extended release matrix tablets using extended release polymers like HPMC K4M, HPMC K15M and HPMC K100M, Metalose 60 SH-50 and Xanthum gum in different concentrations. Formulated tablets were characterized for different parameters like hardness, thickness, weight variation, friability, % Cumulative drug release etc. Nine formulations (F1 – F9 were formulated using direct compression technique. From the results obtained, it was concluded that the optimized formulation containing HPMC K15 M and K100M (1:2 showed better release up to 24hrs.The dissolution profiles and kinetic studies indicate that the release of Darifenacin Hydrobromide can be effectively controlled by the use of hydrophilic matrix systems. Different kinetic models were applied to the optimized formulation and observed that formulation (F9 followed first order kinetic model and Non-Fickian diffusion (or Anomalous transport as mechanism of drug release.

  15. Treatment-Continuity of ADHD Compared Using Immediate-Release and Extended-Release MPH

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-07-01

    Full Text Available The continuity of methylphenidate (MPH therapy for ADHD in young Medicaid beneficiaries (ages 6 to 17 years treated with immediate-release (IR or extended-release (ER MPH formulations was compared in an analysis of statewide California Medicaid claims (2000-2003 conducted at Columbia University, New York; University of Pennsylvania, Philadelphia; and McNeil Pharmaceuticals, Fort Washington, PA.

  16. Fluvoxamine in the treatment of compulsive buying.

    Science.gov (United States)

    Black, D W; Monahan, P; Gabel, J

    1997-04-01

    The authors report the results of an open trial of fluvoxamine in the treatment of compulsive buying. Ten nondepressed subjects were recruited through word-of-mouth and rnet restrictive inclusion/exclusion criteria. Subjects were assessed with the Yale-Brown Obsessive-Compulsive Scale modified for compulsive buying, the Clinical Global Impression scale, and other measures. After a single-blind 1-week placebo run-in, subjects received fluvoxamine up to 300 mg daily for 9 weeks. Nine of 10 subjects improved and were less preoccupied with shopping, spent less time shopping, and reported spending less money. We conclude that compulsive buyers can be recruited for research and their symptoms measured and monitored and, finally, that fluvoxamine may be effective in its treatment.

  17. Fluvoxamine in the treatment of tricyclic-resistant depression.

    Science.gov (United States)

    White, K; Wykoff, W; Tynes, L L; Schneider, L; Zemansky, M

    1990-09-01

    Following an initial double-blind, randomized, parallel treatment group comparison of fluvoxamine, desipramine, and placebo in 89 outpatients with major depression at two centers, double-blind crossover to fluvoxamine was offered to 13 of 22 desipramine-treated completers of the initial phase who were considered failures on desipramine. Twelve elected to cross over to blinded fluvoxamine, and eleven continued on fluvoxamine for at least eight weeks. Nine of these eleven improved, and overall there was a statistically significant decrease in average Hamilton Depression Scores, from 24 to 13, for these fluvoxamine-treated desipramine-resistant patients.

  18. Pharm GKB: fluvoxamine [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available e debrisoquine desipramine dextromethorphan doxepin duloxetine escitalopram fleca...orpromazine citalopram clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin flec...ine codeine debrisoquine desipramine dextromethorphan doxepin duloxetine escitalopram flecainide fluoxetine ... clomipramine clozapine codeine debrisoquine desipramine dextromethorphan doxepin duloxetine escitalopram fl...codeine debrisoquine desipramine dextromethorphan doxepin flecainide fluoxetine fluvoxamine gefitinib halope

  19. A fluvoxamine-caffeine interaction study

    DEFF Research Database (Denmark)

    Jeppesen, U; Loft, S; Poulsen, H E

    1996-01-01

    The selective serotonin reuptake inhibitor fluvoxamine is a very potent inhibitor of the liver enzyme CYP1A2, which is the major P450 catalysing the biotransformation of caffeine. Thus, a pharmacokinetic study was undertaken with the purpose of documenting a drug-drug interaction between fluvoxam......The selective serotonin reuptake inhibitor fluvoxamine is a very potent inhibitor of the liver enzyme CYP1A2, which is the major P450 catalysing the biotransformation of caffeine. Thus, a pharmacokinetic study was undertaken with the purpose of documenting a drug-drug interaction between...... fluvoxamine and caffeine. The study was carried out as a randomized, in vivo, cross-over study including eight healthy volunteers. In Period A of the study, each subject took 200 mg caffeine orally, and in Period B, the subjects took fluvoxamine 50 mg per day for 4 days and 100 mg per day for 8 days. On day 8...... in Period B, the subjects again ingested 200 mg caffeine. After caffeine intake, blood and urine were sampled at regular intervals. Caffeine and its three primary demethylated metabolites, paraxanthine, theobromine and theophylline in plasma and the same four compounds plus 11 more metabolites in urine were...

  20. Effect of hydrophilic and hydrophobic polymers on release kinetics of metoprolol succinate extended release tablets

    Directory of Open Access Journals (Sweden)

    Ramani Gade

    2011-01-01

    Full Text Available The purpose of the present work is to design and evaluate extended release matrix tablets of metoprolol succinate to reduce the dosing frequency and to improve patient compliance. The matrix tablets were prepared by the combination of hydrophilic and hydrophobic polymers, using methocel 10000 Cps in combination with ethyl cellulose 7 Cps, Eudragit® RS100, Eudragit® S100, and Eudragit® L100.The tablets were prepared by direct compression technique. Prepared formulations were evaluated for various parameters like weight variation, thickness, hardness, friability, and % drug content. Tablets were subjected to in vitro drug release studies. The formulations containing methocel 10000 Cps, Eudragit® L100 showed good release retardation. All the prepared formulations showed first-order release kinetics with matrix diffusion mechanism of release. The formulation containing 52.06% w/w of methocel 10000 Cps, 8.75% Eudragit® L100 offered the required release rate according to USP Pharmacopoeial guidelines. The combination of hydrophilic and hydrophobic polymers can effectively control the drug release for freely water-soluble drugs in case of extended release formulations which are the upcoming dosage forms for patient compliance in all aspects.

  1. Effect of different polymers on release of ranolazine from extended release tablets

    Directory of Open Access Journals (Sweden)

    T. E. G. K. Murthy

    2013-01-01

    Full Text Available An extended release tablet provides prolonged release of drug, maintains the desired concentration of drug in plasma and thereby reduce dosing frequency, improve patient compliance and reduce the dose-related side-effects. Ranolazine is indicated for the chronic treatment of angina in patients who have not achieved an adequate response with other anti-anginal agent. The present investigation was undertaken to design the extended release tablets of ranolazine employing different polymers as matrix forming agents using direct compression technique. Formulated tablets were evaluated for weight variation, hardness, friability, drug content, swelling index and in vitro release studies. The drug release followed first order kinetics and controlled by both erosion and diffusion mechanism. It is concluded that the desired drug release pattern can be obtained from the formulation containing 9.8% w/w eudragit and 39.2% w/w metallose offered relatively much slow release of ranolazine compared with other formulations. The selected formulation showed a similarity factor 76 when comparing in vitro dissolution data of the commercial formulation ranozex 500.

  2. FORMULATION AND EVALUATION OF EXTENDED RELEASE TABLETS OF TRAMADOL HYDROCHLORIDE

    Directory of Open Access Journals (Sweden)

    Chilvalvar Sapnil

    2013-10-01

    Full Text Available The objective of this research work was to develop extended release tablets (Twice in a day of Tramadol Hydrochloride using different Hydrophilic polymers like HPMC K15M, HPMC K4M, Metalose 60SH50, Carbopol 971P, Sodium alginate, Xanthan gum by direct compression method. Various amounts of polymers was used in the twenty four proposed formulations (F1 to F24 for the study of release rate retardant effect at 10 %, 15 %, 20 %, 25 % of total weight of tablet matrix respectively. Then the tablets were evaluated in terms of their physical parameters (weight variation, hardness, friability and thickness, drug content and in-vitro release studies. All the formulations showed compliance with pharmacopoeial standards. The in-vitro dissolution study were conducted using USP dissolution apparatus type-II (paddle method in 900 ml 0.1 N HCl for first 2 h and remaining 10 h performed in 6.8 pH phosphate buffer at 100 rpm for a total period of 12 h. Based on the dissolution data comparison with innovator product, formulation F14 was found as the best formulation. The drug release of formulation F14 followed First Order kinetic model and the mechanism was found to be non-Fickian/anomalous according to Korsmeyer-Peppas equation.

  3. Lack of a pharmacokinetic drug-drug interaction with venlafaxine extended-release/indinavir and desvenlafaxine extended-release/indinavir.

    Science.gov (United States)

    Jann, Michael W; Spratlin, Vicky; Momary, Kathryn; Zhang, Hailing; Turner, David; Penzak, Scott R; Wright, Alan; VanDenBerg, Chad

    2012-05-01

    To assess the effects of venlafaxine extended-release (XR) capsules and desvenlafaxine extended-release (XR) tablets upon indinavir pharmacokinetic properties when co-administrated to healthy volunteers. This was an open-label, two-period, fixed-dose study conducted at the clinical research unit located on a university campus. Twenty-four healthy volunteers enrolled in the study (mean age 28.3 ± 8.0 years). Each subject received a single dose of indinavir 800 mg on day 1. Subsequently, subjects were then randomly assigned to either the venlafaxine XR group (N = 12) or the desvenlafaxine XR group (N = 12). Starting on day 2, venlafaxine XR was dosed at 37.5 mg/day for 4 days and increased to 75 mg/day for 6 days. Desvenlafaxine XR was dosed at 50 mg/day for 10 days. On day 12, indivanvir 800 mg was co-administered to both the venlafaxine XR and the desvenlafaxine XR groups. The pharmacokinetics of indinavir were determined both before and at the end of antidepressant dosing. Plasma indinavir, venlafaxine, and desvenlafaxine concentrations were assayed by high-performance liquid chromatography with ultra-violet (UV) detection. Indinavir pharmacokinetic parameters were calculated by noncompartmental analysis using validated computer software. Venlafaxine XR and desvenlafaxine XR did not produce any significant changes in indinavir disposition. Both antidepressants were well tolerated by the subjects with only minor adverse side effects. No pharmacokinetic drug-drug interaction was demonstrated between venlafaxine XR and indinavir or between desvenlafaxine XR and indinvair. The lack of interaction could be due to the venlafaxine and desvenlafaxine extended-release formulation.

  4. Effects of Extended-Release Niacin and Extended-Release Niacin/Laropiprant on the Pharmacokinetics of Simvastatin in Healthy Subjects.

    Science.gov (United States)

    Lauring, Brett; Dishy, Victor; De Kam, Pieter-Jan; Crumley, Tami; Wenning, Larissa; Liu, Fang; Sisk, Christine; Wagner, John; Lai, Eseng

    2015-01-01

    The use of multiple lipid-modifying agents with different mechanisms of action is often required to regulate lipid levels in patients with dyslipidemia. During combination therapy, alterations in the pharmacokinetics of any of the drugs used and their metabolites may occur. Three separate open-label, randomized, crossover studies evaluated the potential for pharmacokinetic interaction between extended-release niacin (with and without concomitant laropiprant) and simvastatin in healthy subjects. Study 1 used single doses of extended-release niacin and simvastatin; study 2 used multiple-dose coadministration of extended-release niacin/laropiprant and simvastatin in healthy subjects; and study 3 used single doses of both extended-release niacin and the coadministration of extended-release niacin/laropiprant and simvastatin in healthy Chinese subjects. During each treatment period, plasma samples were collected predose and at prespecified postdose time points for pharmacokinetic analyses. The safety and tolerability of simvastatin with and without coadministered extended-release niacin (or extended-release niacin/laropiprant) were assessed by clinical evaluation of adverse experiences. In 2 studies in healthy subjects, modest increases in exposure to simvastatin acid (by ∼60%) by extended-release niacin and extended-release niacin/laropiprant were observed. Based on the clinical experience with simvastatin, these effects are not believed to be clinically meaningful. In the third study on healthy Chinese subjects, no statistically meaningful increases in exposure to simvastatin by extended-release niacin and extended-release niacin/laropiprant were observed. In all populations examined in these studies, the coadministration of extended-release niacin and simvastatin was generally well tolerated.

  5. Modeling the heterogeneous intestinal absorption of propiverine extended-release.

    Science.gov (United States)

    Weiss, Michael; Sermsappasuk, Pakawadee; Siegmund, Werner

    2015-08-30

    Propiverine is a widely used antimuscarinic drug with bioavailability that is limited by intestinal first-pass extraction. To study the apparent heterogeneity in intestinal first-pass extraction, we performed a population analysis of oral concentration-time data measured after administration of an extended-release formulation of propiverine in ten healthy subjects. Using an inverse Gaussian function as input model, the assumption that the systemically available fraction increases as a sigmoidal function of time considerably improved the fit. The step-like increase in this fraction at time t=3.7h predicted by the model suggests that propiverine is predominantly absorbed in colon. A nearly perfect correlation was found between the estimates of bioavailability and mean dissolution time. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Optimizing extended-release carbidopa/levodopa in Parkinson disease

    Science.gov (United States)

    Pagan, Fernando L.; Walter, Benjamin L.; Morgan, John C.; Elmer, Lawrence W.; Waters, Cheryl H.; Agarwal, Pinky; Dhall, Rohit; Ondo, William G.; Klos, Kevin J.; Silver, Dee E.

    2017-01-01

    Abstract Purpose of review: To help clinicians optimize the conversion of a patient's Parkinson disease pharmacotherapy from immediate-release carbidopa/levodopa (IR CD/LD) to an extended-release formulation (ER CD/LD). Recent findings: Eleven movement disorders specialists achieved consensus positions on the modification of trial-based conversion guidelines to suit individual patients in clinical practice. Summary: Because the pharmacokinetics of ER CD/LD differ from those of IR CD/LD, modification of dosage and dosing frequency are to be expected. Initial regimens may be based on doubling the patient's preconversion levodopa daily dosage and choosing a division of doses to address the patient's motor complications, e.g., wearing-off (warranting a relatively high ER CD/LD dose, possibly at a lower frequency than for IR CD/LD) or dyskinesia (warranting a relatively low dose, perhaps at an unchanged frequency). Patients should know that the main goal of conversion is a steadier levodopa clinical response, even if dosing frequency is unchanged. PMID:28243505

  7. Pharmacokinetic profile of once-daily cyclobenzaprine extended-release.

    Science.gov (United States)

    Darwish, Mona; Hellriegel, Edward T

    2010-11-01

    Cyclobenzaprine immediate-release (CIR) is a widely prescribed skeletal muscle relaxant with an established efficacy and safety profile in patients with muscle spasm associated with acute, painful conditions, although it is commonly associated with sedation. CIR is typically prescribed at a dosage of 10 mg three-times-daily. This review focuses on the pharmacokinetic profile of a new formulation, cyclobenzaprine extended-release (CER), which delivers a sustained plasma cyclobenzaprine concentration over 24 h, allowing once-daily dosing. Results from CER pharmacokinetic studies conducted through August 2010 are summarized. This review provides information on the first four studies assessing the single-dose and steady-state pharmacokinetic profile of CER. Once-daily CER 30 mg and three-times-daily CIR 10 mg produced comparable systemic exposures to cyclobenzaprine, but pharmacokinetic profiles were qualitatively different. CER was characterized by a single daily peak in cyclobenzaprine concentration versus three peaks/day for CIR. With once-daily dosing of CER, cyclobenzaprine concentration is sustained over 24 h. CER 30 mg provides approximately twice the exposure as CER 15 mg. Systemic exposure to CER is increased in the presence of food and in elderly subjects. Steady-state is achieved by day 7 of dosing.

  8. Influence of cellulose derivatives and natural polymers on in vitro release kinetics of metoprolol succinate from extended release matrix tablets

    OpenAIRE

    Sunil, R.; Somagoni, Jagan M.; Panakanti, Pavan K.; Ega, Chandra M.; Yamsani, Madhusudan R.

    2011-01-01

    In the present investigation, extended release tablets of metoprolol succinate were developed using cellulose derivatives and natural gums as matrix formers and were evaluated for its extended release characteristics. The optimized formulation (F7) was obtained using cellulose derivatives in the ratio of 1:0.5:1drug, HPMC K 100M and Na CMC, respectively. Prepared tablets were subjected to all the Pharmacopeial quality tests and found to be in the limits. The in vitro release studies of prepar...

  9. Urinary Incontinence during Sleep Associated with Extended Release Form of Bupropion HCI

    Science.gov (United States)

    Izci, Filiz; Iris Koc, Merve; Bilici, Rabia; Yalcin, Murat; Bestepe, Engin Emrem

    2015-01-01

    Bupropion hydrochloride (HCI) is an antidepressant that acts as a norepinephrine and dopamine reuptake inhibitor and has three different dosage forms including immediate release (IR), sustained release (SR), and extended release (ER). Despite its relatively safe side effect profile bupropion may cause several side effects. Here, we aimed to report a case with major depression using extended release form of bupropion hydrochloride who was presented with urinary incontinence during sleep, an uncommon side effect of bupropion. PMID:26613061

  10. Multiple dose pharmacokinetics of a new once daily extended release tolterodine formulation versus immediate release tolterodine.

    Science.gov (United States)

    Olsson, B; Szamosi, J

    2001-01-01

    To determine the multiple dose pharmacokinetics of a new extended release (ER) capsule formulation of tolterodine, compared with the existing immediate release (IR) tablet, in healthy volunteers. Nonblind, randomised, 2-way crossover trial. 19 healthy volunteers (7 females, 12 males), mean age 33 years (range 18 to 55 years). Prior to the study, all volunteers were classified as either extensive or poor metabolisers by cytochrome P450 2D6 genotyping. Volunteers received tolterodine ER 4mg once daily or tolterodine IR 2mg twice daily for 6 days (all doses given as the L-tartrate salt). A washout period of 7 days separated the 2 treatments. Serum concentrations of tolterodine, its active 5-hydroxymethyl metabolite (5-HM) and the active moiety (extensive metabolisers: sum of unbound tolterodine + 5-HM; poor metabolisers: unbound tolterodine) were measured for up to 48 hours post-dose on day 6 (steady state). Tolerability was also determined. 17 volunteers (13 extensive metabolisers, 4 poor metabolisers) completed the study and were evaluable for both treatment periods. The 90% confidence interval for the geometric mean ratio of area under the serum concentration-time curve to 24 hours (AUC24) of the active moiety, for all volunteers combined, indicated equivalence for the 2 formulations. Pooled analysis also demonstrated that the peak serum concentration (Cmax) of the active moiety following administration of tolterodine ER was around 75% of that observed for the IR tablet, whereas the trough concentration was around 1.5-fold higher. Overall, the pharmacokinetics of tolterodine (irrespective of genotype) and 5-HM (extensive metabolisers only) were consistent with sustained drug release over 24 hours. Tolterodine ER was well tolerated. The new once daily ER formulation of tolterodine 4mg shows pharmacokinetic equivalence (AUC24) to the existing IR tablet given at a dose of 2mg twice daily. Findings of lower Cmax for tolterodine ER may explain the significantly lower

  11. Formulation of Extended-Release Metformin Hydrochloride Matrix ...

    African Journals Online (AJOL)

    Erah

    carrier, polymer and preparation method on metformin release from the formulations in vitro as well as ... Results: The physicochemical characteristics of all the granules and tablets were generally satisfactory. Optimization ..... Some physical.

  12. Metformin extended release--DepoMed: metformin, metformin gastric retention, metformin GR.

    Science.gov (United States)

    2004-01-01

    Metformin extended release [Glumetza, metformin hydrochloride, metformin gastric retention, metformin GR] is a proprietary once-a-day formulation of metformin hydrochloride under development with DepoMed for the treatment of diabetes. In May 2002, DepoMed licensed manufacturing and marketing rights for its proprietary formulation of metformin extended release (500mg dose) to Biovail Corporation for the US (including Puerto Rico) and Canada. Under the terms of the agreement, Biovail would pay a $25 million milestone fee upon approval and also customary royalties on the net sales in the US and Canada. Biovail also agreed to acquire approximately 2.4 million of additionally issued DepoMed shares for $12.3 million. Biovail has subsequently developed a 1000mg dose of metformin extended release. In April 2004, Depomed and Biovail amended their original license agreement of May 2002. Under the terms of the amended agreement, Depomed will receive royalties on sales of Biovail's 1000mg tablet in the US and Canada. In turn, Biovail acquired access to Depomed's clinical data for the metformin 500mg tablet that will be used to accelerate regulatory filings for Biovail's 1000mg tablet and establish equivalence between the two dosages. Metformin GR is available for partnership in Europe and Asia (Bio-Square-2004, Basel, Switzerland). In April 2004, Depomed and Biovail filed an NDA with the US FDA for the once-daily, extended-release formulation of metformin extended release (Glumetza), 500mg and 1000mg tablets. The 500mg dosage was developed by Depomed using its patented drug delivery GR technology, while Biovail developed the metformin 1000mg dose using its proprietary Smartcoat delivery technology. Depomed completed two double-blind, pivotal, phase III clinical trials with metformin extended release 500mg at 60 sites in the US in more than 1000 patients with type 2 diabetes. In three different dosing regimens, metformin extended release significantly decreased the glycosylated

  13. Effects of calcium channel blocker, nifedipine, on antidepressant activity of fluvoxamine, venlafaxine and tianeptine in mice

    Directory of Open Access Journals (Sweden)

    Ashok K. Sharma

    2015-02-01

    Conclusions: Nifedipine, fluvoxamine, venlafaxine and tianeptine possess antidepressant activity and nifedipine exhibits synergistic antidepressant activity with fluvoxamine, venlafaxine and tianeptine. [Int J Basic Clin Pharmacol 2015; 4(1.000: 82-88

  14. Hydroxypropyl methylcellulose based cephalexin extended release tablets: influence of tablet formulation, hardness and storage on in vitro release kinetics.

    Science.gov (United States)

    Saravanan, Muniyandy; Sri Nataraj, Kalakonda; Ganesh, Kettavarampalayam Swaminath

    2003-08-01

    The object of this study was to develop hydroxypropyl methylcellulose (HPMC) based cephalexin extended release tablet, which can release the drug for six hours in predetermined rate. Twenty-one batches of cephalexin tablets were prepared by changing various physical and chemical parameters, in order to get required theoretical release profile. The influences of HPMC, microcrystalline cellulose powder (MCCP), granulation technique, wetting agent and tablet hardness on cephalexin release from HPMC based extended release tablets were studied. The formulated tablets were also characterized by physical and chemical parameters. The dissolution results showed that a higher amount of HPMC in tablet composition resulted in reduced drug release. Addition of MCCP resulted in faster drug release. Tablets prepared by dry granulation was released the drug slowly than the same prepared with a wet granulation technique. Addition of wetting agent in the tablets prepared with dry granulation technique showed slower release. An increase in tablet hardness resulted in faster drug release. Tablets prepared with a wet granulation technique and having a composition of 9.3% w/w HPMC with a hardness of 10-12 kg/cm(2) gave predicted release for 6 h. The in vitro release data was well fit in to Higuchi and Korsmeyer-Peppas model. Physical and chemical parameters of all formulated tablets were within acceptable limits. One batch among formulated twenty-one batches was successful and showed required theoretical release. The effect of storage on in vitro release and physicochemical parameters of successful batch was studied and was found to be in acceptable limits.

  15. Reduced cognitive and psychomotor impairment with extended-release oxymorphone versus controlled-release oxycodone.

    Science.gov (United States)

    Schoedel, Kerri A; McMorn, Stephen; Chakraborty, Bijan; Zerbe, Kathleen; Sellers, Edward M

    2010-01-01

    Opioids provide effective pain control, yet have risks including adverse events (AEs) (e.g., constipation, nausea/vomiting, sedation) and cognitive/psychomotor effects. To compare cognitive and psychomotor effects of oxymorphone extended release (OM-ER) versus oxycodone controlled release (OC-CR). Randomized, double-blind, 5-way crossover Single inpatient research unit Nondependent recreational opioid users were administered single intact oral tablets of placebo, OM-ER (15 and 30 mg), and OC-CR (30 and 60 mg), separated by a 7- to 21-day washout. The divided attention (DA) test measured psychomotor impairment (e.g., manual tracking [e.g., percentage over road], target accuracy [e.g., target hits], reaction time [hit latency]). Visual analog scales measured alertness/drowsiness, agitation/relaxation, and dizziness. Sedative, stimulant, and dysphoric effects were measured using the Addiction Research Center Inventory Pentobarbital-Chlorpromazine-Alcohol (PCAG), Benzedrine Group (BG), and Lysergic Acid Diethylamide (LSD) scales, respectively. Comparisons were made between equianalgesic doses (OM-ER 15 mg vs OC-CR 30 mg; OM-ER 30 mg vs OC-CR 60 mg), within active drug doses, and between active drugs and placebo using least squares (LS) mean difference of the peak maximum (Emax) or minimum (Emin) effect using linear mixed model analysis of covariance. Thirty-five participants received all 5 treatments. Peak cognitive and psychomotor impairment (LS mean [SE]) was less with OM-ER than equianalgesic doses of OC-CR for reaction time (Emax hit latency, longer if impaired; 571.2 [13.4] vs 588.1 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], PLSD, P<0.001 for both equianalgesic dose groups), and sedation (Emax, PCAG; P<0.001 for both equianalgesic dose groups) and less stimulation (BG, Emin; P=0.01 for OM-ER 15 mg vs OC-CR mg; P<0.001 for OM

  16. Dexmethylphenidate Extended-Release Capsules in Children with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Silva, Raul R.; Muniz, Rafael; Pestreich, Linda; Brams, Matthew; Mao, Alice R.; Childress, Ann; Wang, James

    2008-01-01

    A study to compare the release of 20mg of dexmethylphenidate extended-release capsules against placebo spread over a period of 12 hours in children afflicted with attention-deficit/hyperactivity disorder (ADHD) is conducted. Findings reveal that dexmethylphenidate provided significant improvement.

  17. Role of hydroxypropylmethylcellulose (HPMC 4000 in the protection of the polymorphs of Piroxicam extended release tablets

    Directory of Open Access Journals (Sweden)

    A. Merah

    2017-02-01

    The physico-chemical tests and the dissolution profiles of polymorphs and tablets showed that the metolose incorporated in the tablets at a rate equivalent to 5% could possibly act doubly; initially by protecting the piroxicam polymorphism transition (form II during compression, then modulating its in vitro release (extended release.

  18. Pharmacological and clinical evidence of nevirapine immediate- and extended-release formulations

    Directory of Open Access Journals (Sweden)

    Ena J

    2012-11-01

    Full Text Available Javier Ena, Concepción Amador, Conxa Benito, Francisco PasquauHIV Unit, Hospital Marina Baixa, Villajoyosa, SpainAbstract: We reviewed the current information available on nevirapine immediate- and extended-release formulations and its role in single-dose and combination antiretroviral therapy. Nevirapine was approved in 1996 and was the first non-nucleoside reverse-transcriptase inhibitor available for the treatment of HIV-1 infection. Nevirapine has demonstrated good efficacy and a well-characterized safety profile. A major drawback is the low genetic barrier, allowing the emergence of resistance in the presence of single mutations in the reverse-transcriptase gene. This shortcoming is particularly relevant when nevirapine is administered in a single dose to prevent mother-to-child transmission of HIV-1 infection, compromising the efficacy of future non-nucleoside reverse transcriptase–inhibitor regimens. Studies published recently have probed the noninferiority of nevirapine compared to ritonavir-boosted atazanavir with both tenofovir disoproxil fumarate and emtricitabine in antiretroviral treatment–naïve patients. In 2011, a new formulation of nevirapine (nevirapine extended release that allowed once-daily dosing was approved by the Food and Drug Administration and by the European Medicines Agency. VERxVe, a study comparing nevirapine extended release with nevirapine immediate release in antiretroviral treatment–naïve patients, and TRANxITION, a study carried out in antiretroviral treatment–experienced patients who switched therapy from nevirapine immediate release to nevirapine extended release, provided data on the noninferiority of the new formulation of nevirapine compared with nevirapine immediate release in terms of efficacy and safety. Nevirapine extended release will further increase the durability and persistence of nevirapine-containing antiretroviral therapy, allowing once-daily dosing regimens.Keywords: nevirapine

  19. Surveillance of Diversion and Nonmedical Use of Extended-Release Prescription Amphetamine and Oral Methylphenidate in the United States

    OpenAIRE

    Sembower, Mark A.; Ertischek, Michelle D.; Buchholtz, Chloe; Dasgupta, Nabarun; Schnoll, Sidney H.

    2013-01-01

    This article examines rates of nonmedical use and diversion of extended-release amphetamine and extended-release oral methylphenidate in the United States. Prescription dispensing data were sourced from retail pharmacies. Nonmedical use data were collected from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Drug Diversion Program and Poison Center Program. Drug diversion trends nearly overlapped for extended-release amphetamine and extended-release oral met...

  20. Extended-release niacin alters the metabolism of plasma apolipoprotein (apo) A-I- and apoB-containing lipoproteins

    Science.gov (United States)

    Extended-release niacin effectively lowers plasma TG levels and raises plasma HDL cholesterol levels, but the mechanisms responsible for these effects are unclear. We examined the effects of extended-release niacin (2 g/d) and extended-release niacin (2 g/d) plus lovastatin (40 mg/d), relative to pl...

  1. FORMULATION AND EVALUATION OF EXTENDED RELEASE MATRIX TABLETS OF TRIMETAZIDINE DIHYDROCHLORIDE

    Directory of Open Access Journals (Sweden)

    Mogili Dinesh

    2013-01-01

    Full Text Available Oral ingestion has long been the most convenient and commonly employed route of drug delivery. Indeed, for Extended release systems, the oral route of administration has by far received the most attention with respect to research on physiological and drug constraints as well as design and testing of products. The primary objective of the extended release (Matrix drug delivery system is to ensure safety and to improve efficacy of drug as well as patient compliance. The present invention provides a novel sustained release composition comprising Trimetazidine Dihydrochloride. The objective of the present study was to formulate and evaluate once daily extended release matrix tablets of Trimetazidine Dihydrochloride using hydrophilic polymers Hydroxypropylmethylcellulose, Polyox, and natural polymer Xanthan gum. Trimetazidine has a half life 6 hrs and usual oral dosage regimen 0.5 mg and 60 mg daily. To reduce the frequency of administration and to improve patient compliance, a once-daily extended release formulation of Trimetazidine is desirable. The most commonly used method of modulating the drug release is to include it in a matrix system. Hydrophilic polymer matrix systems were widely used in oral controlled drug delivery because they make it easier to achieve a desirable drug-release profile, they are cost effective and they have broad US Food and Drug Administration acceptance. Hence, in present work, an attempt has been made to develop once daily sustained release matrix tablets of Trimetazidine using putative hydrophilic matrix materials. The drug release for extended duration using a hydrophilic matrix system is restricted because of rapid diffusion of dissolved drug through the hydrophilic gel network.

  2. DEVELOPMENT OF A NOVEL ENTERIC COATED EXTENDED RELEASE PELLETS USING MODEL NSAID FLURBIPROFEN

    Directory of Open Access Journals (Sweden)

    V. Abhinetri, Mohd. Abdul Hadi*, A. Srinivasa Rao and Sravani V.

    2013-02-01

    Full Text Available The aim of this study was to develop a pH responsive enteric coated extended release pellets containing a model drug flurbiprofen, a non-steroidal anti-inflammatory drug used for rheumatoid arthritis. The drug loaded pellets were prepared by using extrusion/ spheronization method. Core pellets were coated with polymer Eudragit RS30D in a coating pan to achieve a sustainable release for 12 hours. A ph responsive barrier coat of Eudragit L 100-55 was employed in a coating pan for abstaining release in acidic media. The drug excipient mixtures were subjected to pre-formulation studies. The pellets were subjected to physicochemical studies, in-vitro drug release, Kinetic studies and stability studies. FTIR studies shown there was no interaction between drug and polymers. The physicochemical properties of pellets were found within the limits. The drug release from the optimized formulations was extended for a period of 12 hrs i.e. first 2 hrs no drug release was observed and gradually drug release was increased up to 12 hrs. From the above results, achievement of site specific release to lower part of gastrointestinal tract might be due to Eudragit L 100-55 stability in acidic pH. The prepared pellets apart from fulfilling all official and other specifications, exhibited good extended release of Flurbiprofen. The optimized formulations were subjected to stability studies and shown there were no significant changes in drug content, physicochemical parameters and release pattern. In conclusion, development of Eudragit RS30D-Eudragit L 100-55 was novel and good approach to achieve the site specific release of drug to colon.

  3. Formulation and evaluation of ranolazine extended release tablets: Influence of polymers

    Directory of Open Access Journals (Sweden)

    TEGK Murthy

    2011-01-01

    Full Text Available An extended release tablet provides prolonged periods of drug in plasma levels thereby reduce dosing frequency, improve patient compliance and reduce the dose-related side effects. Ranolazine is indicated for the chronic treatment of angina in patients who have not achieved an adequate response with other anti-anginal agents. The present investigation was undertaken to design extended release tablets of Ranolazine employing hypromellose phthalate grade HP-55, ethocel standard 7FP premium ethyl cellulose, Surelease E-7-19040, Klucel HF pharm and Natrosol Type 250 HHX as matrix forming agents using wet granulation method. Formulated tablets were evaluated for uniformity of weight, assay, water content, in vitro drug release studies and stability studies. The drug release followed first order kinetics with both erosion and diffusion as the release mechanism. It is concluded that the desired drug release pattern can be obtained by using natrosol type 250 HHX compared to other polymers. The similarity factor (f2 was calculated to select best formulation by comparing in vitro dissolution data of the commercial formulation Ranexa® . The formulated tablets fulfilled the compendia requirements. The formulated Ranolazine Extended release tablets were found to be stable.

  4. Euprolactinemic gynecomastia and galactorrhea with risperidone-fluvoxamine combination.

    Science.gov (United States)

    Pratheesh, P J; Praharaj, Samir Kumar; Srivastava, Ashish

    2011-01-01

    Risperidone is associated with hyperprolactinemia and its consequent symptoms such as gynecomastia, galactorrhea and sexual dysfunction in adults, and less so in adolescents. Rarely, serotonin reuptake inhibitors are also associated with such adverse effects. We report a case of gynecomastia and galactorrhea in an adolescent male while on a combination of risperidone and fluvoxamine, although the serum prolactin was within normal range.

  5. Development and Evaluation of Extended Release Formulation of Tramadol Hydrochloride Based on Osmotic Technology

    Directory of Open Access Journals (Sweden)

    Patel JB

    2013-05-01

    Full Text Available Extended release formulation of Tramadol Hydrochloride based on osmotic technology was developedand evaluated. Target release profile was selected and different variables were optimized to achieve it.Formulation variables such as osmotic agent, plasticizer and coating thickness of semi-permeablemembrane were found to markedly affect drug release. Tramadol hydrochloride release was directlyproportional to the level of osmogent and plasticizer but inversely proportional to the level of coatingthickness of semi-permeable membrane. Drug release from developed formulation was independent ofpH and agitation intensity but dependent on osmotic pressure of release media. The optimizedformulation was compared with marketed product CONTRAMAL SR and accelerated stability studywas also carried out for 6 months.

  6. Auditory musical hallucinations associated with extended-release pramipexole in an elderly patient with Parkinson's disease.

    Science.gov (United States)

    Kataoka, Hiroshi; Ueno, Satoshi

    2014-12-01

    Auditory musical hallucinations (AMHs) are rare complex auditory hallucinations in Parkinson's disease (PD) that have been limited previously. The characteristics of AMHs in PD remain uncertain. We describe a 72-year-old woman with PD who presented with AMHs. The AMHs occurred after immediate-release pramipexole was switched to extended-release pramipexole. The AMHs were a quiet piano or often songs on a loud radio or background music over other sounds. The music was unpleasant, but not objectionable, threatening, or ego-syntonic, and it did not interrupt her daily activities. AMHs in PD were non-threatening, and dopaminergic treatment may predispose patients to AMHs or be a unique possible cause of AMHs. The hallucinations can occur after immediate-release pramipexole was switched to extended-release pramipexole.

  7. Auditory Musical Hallucinations Associated With Extended-Release Pramipexole in an Elderly Patient With Parkinson's Disease

    OpenAIRE

    Kataoka, Hiroshi; Ueno, Satoshi

    2014-01-01

    Abstract Auditory musical hallucinations (AMHs) are rare complex auditory hallucinations in Parkinson's disease (PD) that have been limited previously. The characteristics of AMHs in PD remain uncertain. We describe a 72-year-old woman with PD who presented with AMHs. The AMHs occurred after immediate-release pramipexole was switched to extended-release pramipexole. The AMHs were a quiet piano or often songs on a loud radio or background music over other sounds. The music was unpleasant, but ...

  8. Design and development of bilayer tablet for immediate and extended release of acarbose and metformin HCl

    OpenAIRE

    Meenakshi Joshi; Ruchi Tiwari; Gaurav Tiwari

    2014-01-01

    The present investigation studied a novel Bilayer tablet having extended release (ER) system of metformin HCl (M.HCl) with Eudragit RS 100 and RL 100 and immediate release (IR) system of Acarbose with PVP K30 and PEG 6000 in different ratios using solvent evaporation technique. Solid dispersions (SDs) were characterized by Fourier Transform-Infra Red spectroscopy, Diffrential Scanning Calorimetry, X-Ray Diffractometry and Scanning Electron Microscopy. Selected SD system was subjected to Bilay...

  9. Maintaining remission in ulcerative colitis--role of once daily extended-release mesalamine.

    Science.gov (United States)

    Oliveira, Lilliana; Cohen, Russell D

    2011-02-27

    The aminosalicylates (5-ASA; also referred to as mesalamine-based agents) are considered as first-line in the maintenance of remission of mild to moderate ulcerative colitis (UC). Traditionally these agents have required a large pill burden and multiple daily dosing regimens which may account for the low adherence rates, especially in patients in remission. Extended-release mesalamine is the first once daily mesalamine product approved by the Food and Drug Administration for the maintenance of UC remission. This review will examine the pharmacokinetics, dosing, efficacy, and safety data of extended-release mesalamine, and discuss the potential role of improving medication compliance and decreasing costs in UC maintenance.

  10. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

    DEFF Research Database (Denmark)

    Sacco, Ralph L; Diener, Hans-Christoph; Yusuf, Salim

    2008-01-01

    BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly...... assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes...

  11. Formulation and evaluation of once daily minocycline hydrochloride extended release matrix tablets

    Directory of Open Access Journals (Sweden)

    Keny R

    2009-01-01

    Full Text Available The present study was aimed to develop once daily extended release matrix tablets of minocycline hydrochloride, using hydroxypropylmethylcellulose either alone or in combination with ethyl cellulose as the matrix material in different proportions. The formulated tablets were also compared with a marketed product. The results of the dissolution study indicate that formulations FC-IV, FC-V and FC-VI showed maximum drug release upto 24 h, whereas the marketed product was found to extend the release only up to 14 h. Incase of formulations containing combination of hydroxypropylmethylcellulose and ethyl cellulose (FC-I to FC-IX, the release of the drug was found to be dependent on the relative proportions of hydroxypropylmethylcellulose and ethyl cellulose used in the tablet matrix. Mathematical treatment of the in vitro drug release data suggests that, all the formulations best fitted into first order release kinetics. Drug release from the matrix occurred by combination of two mechanisms, diffusion of drug from tablet matrix and erosion of tablet surface, which was reflected from Higuchi′s model and Erosion plot.

  12. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

    NARCIS (Netherlands)

    Sacco, Ralph L.; Diener, Hans-Christoph; Yusuf, Salim; Cotton, Daniel; Ounpuu, Stephanie; Lawton, William A.; Palesch, Yuko; Martin, Renee H.; Albers, Gregory W.; Bath, Philip; Bornstein, Natan; Chan, Bernard P. L.; Chen, Sien-Tsong; Cunha, Luis; Dahlof, Bjorn; De Keyser, Jacques; Donnan, Geoffrey A.; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

    2008-01-01

    Background: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens - aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. Methods: In this double-blind, 2-by-2 factorial trial, we randomly a

  13. Simulated Driving Changes in Young Adults with ADHD Receiving Mixed Amphetamine Salts Extended Release and Atomoxetine

    Science.gov (United States)

    Kay, Gary G.; Michaels, M. Alex; Pakull, Barton

    2009-01-01

    Background: Psychostimulant treatment may improve simulated driving performance in young adults with attention-deficit/hyperactivity disorder (ADHD). Method: This was a randomized, double-blind, placebo-controlled, crossover study of simulated driving performance with mixed amphetamine salts--extended release (MAS XR) 50 mg/day (Cohort 1) and…

  14. Recent advances of starch-based excipients used in extended-release tablets: a review.

    Science.gov (United States)

    Hong, Yan; Liu, Guodong; Gu, Zhengbiao

    2016-01-01

    In recent years, polysaccharides, including starch and its derivatives, have been widely used in the pharmaceutical industry, including as diluents, fillers, binders, disintegrants and glidants. The use of native starch as excipient in extended-release tablets is limited due to its low compactibility and enzymatic degradability, leading to the formation of weakly structured tablets. To overcome these limitations and expand the application of starch as an excipient, researchers have modified starch by physical and chemical methods, as well as by enzymatic hydrolysis. Some starch derivatives, including retrograded starch, pregelatinized starch, carboxymethyl starch, starch acetate, cross-linked starch and grafted starch have recently been introduced as excipients in oral tablets to control drug release. In this review, applications of starch and its derivatives as extended release excipients are reviewed and future frontiers are described.

  15. Extended-release morphine sulfate in treatment of severe acute and chronic pain

    Directory of Open Access Journals (Sweden)

    Robert J Balch

    2010-09-01

    Full Text Available Robert J Balch, Andrea TrescotDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA USAAbstract: Morphine is the archetypal opioid analgesic. Because it is a short-acting opioid, its use has been limited to the management of acute pain. The development of extended-release formulations have resulted in the increased utilization of morphine in chronic pain conditions. This review documents the history of morphine use in pain treatment, and describes the metabolism, pharmacodynamics, formulations, and efficacy of the currently available extended-release morphine medications.Keywords: Morphine ER, sustained-release morphine, MSContin, Oramorph®, Kadian®, Avinza®, Embeda®

  16. Drug delivery and therapeutic impact of extended-release acetylsalicylic acid.

    Science.gov (United States)

    Bliden, Kevin P; Patrick, Jeff; Pennell, Andrew T; Tantry, Udaya S; Gurbel, Paul A

    2016-01-01

    Current treatment guidelines recommend once-daily, low-dose acetylsalicylic acid (ASA; aspirin) for secondary prevention of cardiovascular events. However, the anti-thrombotic benefits of traditional ASA formulations may not extend over a 24-h period, especially in patients at high risk for a recurrent cardiovascular event. A next-generation, extended-release ASA formulation (ER-ASA) has been developed to provide 24-h anti-thrombotic coverage with once-daily dosing. The pharmacokinetics of ER-ASA indicates slower absorption and prolonged ASA release versus immediate-release ASA, with a favorable safety profile. ER-ASA minimizes systemic ASA absorption and provides sustained antiplatelet effects over a 24-h period.

  17. Mathematical Model-Based Accelerated Development of Extended-release Metformin Hydrochloride Tablet Formulation.

    Science.gov (United States)

    Chen, W; Desai, D; Good, D; Crison, J; Timmins, P; Paruchuri, S; Wang, J; Ha, K

    2016-08-01

    A computational fluid dynamic (CFD) model was developed to predict metformin release from a hydroxypropylmethylcellulose (HPMC) matrix-based extended-release formulation that took into consideration the physical and chemical properties of the drug substance, composition, as well as size and shape of the tablet. New high dose strength (1000 mg) tablet geometry was selected based on the surface area/volume (SA/V) approach advocated by Lapidus/Lordi/Reynold to obtain the desired equivalent metformin release kinetics. Maintaining a similar SA/V ratio across all extended-release metformin hydrochloride (Met XR) tablet strengths that had different geometries provided similar simulations of dissolution behavior. Experimental dissolution profiles of three lots of high-strength tablets agreed with the simulated release kinetics. Additionally, a pharmacokinetic absorption model was developed using GastroPlus™ software and known physicochemical, pharmacokinetic, and in vitro dissolution properties of metformin to predict the clinical exposure of the new high strength (1000 mg) tablet prior to conducting a human clinical bioequivalence study. In vitro metformin release kinetics were utilized in the absorption model to predict exposures in humans for new 1000-mg Met XR tablets, and the absorption model correctly projected equivalent in vivo exposure across all dose strengths. A clinical bioequivalence study was pursued based on the combined modeling results and demonstrated equivalent exposure as predicted by the simulations.

  18. Formulation Development and Stability Studies of Norfloxacin Extended-Release Matrix Tablets

    Directory of Open Access Journals (Sweden)

    Paulo Renato Oliveira

    2013-01-01

    Full Text Available The aim of this research was to develop a new hydrophilic matrix system containing norfloxacin (NFX. Extended-release tablets are usually intended for once-a-day administration with benefits to the patient and lower discontinuation of the therapy. Formulations were developed with hydroxypropylmethylcellulose or poly(ethylene oxide as hydrophilic polymers, with different molecular weights (MWs and concentrations (20 and 30%. The tablets were found to be stable (6 months at 40±2°C and 75±5% relative humidity, and the film-coating process is recommended to avoid NFX photodegradation. The dissolution profiles demonstrated an extended-release of NFX for all developed formulations. Dissolution curves analyzed using the Korsmeyer exponential equation showed that drug release was controlled by both drug diffusion and polymer relaxation or erosion mechanisms. A more erosion controlled system was obtained for the formulations containing lower MW and amount of polymer. With the increase in both MW and amount of polymer in the formulation, the gel layer became stronger, and the dissolution was more drug-diffusion dependent. Formulations containing intermediate MW polymers or high concentration (30% of low MW polymers demonstrated a combination of extended and complete in vitro drug release. This way, these formulations could provide an increased bioavailability in vivo.

  19. Formulation Development and Stability Studies of Norfloxacin Extended-Release Matrix Tablets

    Science.gov (United States)

    Oliveira, Paulo Renato; Klein, Lilian; Sangoi, Maximiliano da Silva; Bernardi, Larissa Sakis; Silva, Marcos Antônio Segatto

    2013-01-01

    The aim of this research was to develop a new hydrophilic matrix system containing norfloxacin (NFX). Extended-release tablets are usually intended for once-a-day administration with benefits to the patient and lower discontinuation of the therapy. Formulations were developed with hydroxypropylmethylcellulose or poly(ethylene oxide) as hydrophilic polymers, with different molecular weights (MWs) and concentrations (20 and 30%). The tablets were found to be stable (6 months at 40 ± 2°C and 75 ± 5% relative humidity), and the film-coating process is recommended to avoid NFX photodegradation. The dissolution profiles demonstrated an extended-release of NFX for all developed formulations. Dissolution curves analyzed using the Korsmeyer exponential equation showed that drug release was controlled by both drug diffusion and polymer relaxation or erosion mechanisms. A more erosion controlled system was obtained for the formulations containing lower MW and amount of polymer. With the increase in both MW and amount of polymer in the formulation, the gel layer became stronger, and the dissolution was more drug-diffusion dependent. Formulations containing intermediate MW polymers or high concentration (30%) of low MW polymers demonstrated a combination of extended and complete in vitro drug release. This way, these formulations could provide an increased bioavailability in vivo. PMID:24083235

  20. Gastroretentive extended release of metformin from methacrylamide-g-gellan and tamarind seed gum composite matrix.

    Science.gov (United States)

    Priyadarshini, Rosy; Nandi, Gouranga; Changder, Abhijit; Chowdhury, Sailee; Chakraborty, Sudipta; Ghosh, Lakshmi Kanta

    2016-02-10

    Formulation of a gastroretentive extended release tablet of metformin based on polymethacrylamide-g-gellan (Pmaa-g-GG)-tamarind seed gum (TSG) composite matrix is the main purpose of this study. Tablets were prepared employing wet granulation method taking amount of Pmaa-g-GG, TSG and NaHCO3 (SBC, buoyancy contributor) as independent formulation variables. The tablets were then evaluated for in vitro drug release, buoyancy, ex vivo mucoadhesion, swelling and surface morphology. Compatibility between drug and excipients was checked by DSC, FTIR and XRD analysis. Buoyancy-lag-time, mucoadhesive strength, % drug release and release-rate constant were statistically analyzed using Design-Expert software (version 9.0.4.1) and the formulation was then numerically optimized to obtain USP-reference release profile. The optimized formulation showed excellent buoyancy over a 10h period with buoyancy lag time of 2.76min, significant mucoadhesion and drug release over a period of 10h with f2=71.58. Kinetic modeling unveiled anomalous non-Fickian transport based drug release mechanism.

  1. Critical appraisal of extended-release hydrocodone for chronic pain: patient considerations

    Directory of Open Access Journals (Sweden)

    Gould HJ III

    2015-10-01

    Full Text Available Harry J Gould III,1,3–7 Dennis Paul1–8 1Department of Neurology, 2Department of Pharmacology and Experimental Therapeutics, 3Department of Internal Medicine, Section of Physical Medicine and Rehabilitation, 4Department of Anesthesiology, 5Neuroscience Center of Excellence, 6Center of Excellence for Oral and Craniofacial Biology, 7Pain Mastery Center of Louisiana, 8Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, USA Abstract: Opioid analgesics are currently the most effective pharmacologic option for the management of both acute and chronic forms of moderate-to-severe pain. Although the “as-needed” use of immediate-release formulations is considered optimum for treating acute, painful episodes of limited duration, the scheduled dosing of extended-release formulations with immediate-release supplementation for breakthrough pain is regarded to be most effective for managing chronic conditions requiring around-the-clock treatment. The recent introduction of extended-release formulations of the opioid analgesic hydrocodone potentially broadened the possibility of providing pain relief for individuals for whom current formulations are either ineffective or not tolerated. However, reaction to the approval of the new formulations has fueled controversy over the general safety and need for opioid medications, in light of their potential for misuse, abuse, diversion, and addiction. Here, we discuss how the approval of extended-release formulations of hydrocodone and the emotionally charged controversy over their release may affect physician prescribing and the care available to patients in need of chronic opioid therapy for the management of pain. Keywords: opioid analgesics, patient risks, patient benefits, misuse, addiction

  2. Evaluation of Prosopis africana Seed Gum as an Extended Release Polymer for Tablet Formulation.

    Science.gov (United States)

    Nadaf, Sameer; Nnamani, Petra; Jadhav, Namdeo

    2015-06-01

    In the present work, an attempt has been made to screen Prosopis africana seed gum (PG), anionic polymer for extended release tablet formulation. Different categories of drugs (charge basis) like diclofenac sodium (DS), chlorpheniramine maleate (CPM), and ibuprofen (IB) were compacted with PG and compared with different polymers (charge basis) like xanthan gum (XG), hydroxypropyl methyl cellulose (HPMC-K100M), and chitosan (CP). For each drug, 12 batches of tablets were prepared by wet granulation technique, and granules were evaluated for flow properties, compressibility, and compactibility by Heckel and Leuenberger analysis, swelling index, in vitro dissolution studies, etc. It has been observed that granules of all batches showed acceptable flowability. According to Heckel and Leuenberger analysis, granules of PG-containing compacts showed similar and satisfactory compressibility and compactibility compared to granules of other polymers. PG showed significant swelling (P < 0.05) compared to HPMC, and better than CP and XG. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) study showed no interaction between drugs and polymers. From all PG-containing compacts of aforesaid drugs, drug release was sustained for 12 h following anomalous transport. Especially, polyelectrolyte complex formation retarded the release of oppositely charged drug (CPM-PG). However, extended release was noted in both anionic (DS) and nonionic (IB) drugs, maybe due to swollen gel. All compacts were found to be stable for 3-month period during stability study. This concludes that swelling and release retardation of PG has close resemblance to HPMC, so it can be used as extended release polymer for all types of drugs.

  3. Profile of extended-release oxycodone/acetaminophen for acute pain.

    Science.gov (United States)

    Bekhit, Mary Hanna

    2015-01-01

    This article provides a historical and pharmacological overview of a new opioid analgesic that boasts an extended-release (ER) formulation designed to provide both immediate and prolonged analgesia for up to 12 hours in patients who are experiencing acute pain. This novel medication, ER oxycodone/acetaminophen, competes with current US Food and Drug Administration (FDA)-approved opioid formulations available on the market in that it offers two benefits concurrently: a prolonged duration of action, and multimodal analgesia through a combination of an opioid (oxycodone) with a nonopioid component. Current FDA-approved combination analgesics, such as Percocet (oxycodone/acetaminophen), are available solely in immediate-release (IR) formulations.

  4. Design and evaluation of controlled onset extended release multiparticulate systems for chronotherapeutic delivery of ketoprofen

    Directory of Open Access Journals (Sweden)

    Shivakumar H

    2006-01-01

    Full Text Available An oral controlled onset extended release dosage form intended to approximate the chronobiology of rheumatoid arthritis is proposed for site-specific release to the colon. The multiparticulate system consisting of drug-loaded cellulose acetate cores encapsulated within Eudragit S-100 microcapsules was designed for chronotherapeutic delivery of ketoprofen. Drug-loaded cellulose acetate cores were prepared by emulsion solvent evaporation technique in an oily phase at different drug:polymer ratios (1:1, 2:1 and 4:1. These cores were successfully microencapsulated with Eudragit S-100 following the same technique at the core:coat ratio of 1:5. Scanning electron microscopy (SEM revealed that the cellulose acetate cores were discrete, uniform and spherical with a porous and rough surface, whereas the Eudragit microcapsules were discrete and spherical with a smooth and dense surface. In vitro drug release studies of the Eudragit microcapsules were performed in different pH conditions following pH-progression method for a period of 16 h. The release studies indicated that the microcapsules posses both pH-sensitive and controlled-release properties, showing limited drug release below pH 7.0 (6.40 to 8.94%, following which the cellulose acetate cores effectively controlled the drug release for a period of 11 h in pH 7.5. The differential scanning calorimetric and powder X-ray diffraction studies demonstrated that ketoprofen was present in dissolved state in the cellulose acetate polymeric matrix, which could explain the controlled drug release from the cores. The release of ketoprofen from Eudragit microcapsules in pH 7.5 depended on the cellulose acetate levels and was characterized by Higuchi′s diffusion model.

  5. Fission-gas release at extended burnups: effect of two-dimensional heat transfer

    Energy Technology Data Exchange (ETDEWEB)

    Tayal, M. [Atomic Energy of Canada Limited, Mississauga, Ontario (Canada); Yu, S.D. [Ryerson Polytechnic Univ., Toronto, Ontario (Canada); Lau, J.H.K

    2000-09-01

    To better simulate the performance of high-burnup CANDU fuel, a two-dimensional model for heat transfer between the pellet and the sheath has been added to the computer code ELESTRES. The model covers four relative orientations of the pellet and the sheath and their impacts on heat transfer and fission-gas release. The predictions of the code were compared to a database of 27 experimental irradiations involving extended burnups and normal burnups. The calculated values of fission gas release matched the measurements to an average of 94%. Thus, the two-dimensional heat transfer model increases the versatility of the ELESTRES code to better simulate fuels at normal as well as at extended burnups. (author)

  6. Rhabdomyolysis following Acute Extended-Release Quetiapine Poisoning: A Case Report

    Directory of Open Access Journals (Sweden)

    Antonios Liolios

    2012-01-01

    Full Text Available Background. During the past few years, there have been a number of case reports concerning rhabdomyolysis following quetiapine poisoning; however, there has been none concerning the medication in its extended-release form. Methods. We present the case report of a 48-year-old man presenting a major depressive disorder and borderline personality disorder, who after voluntary intoxication with 12000 mg of quetiapine extended-release developed signs of acute rhabdomyolysis. Results. The rhabdomyolysis was confirmed by the laboratory and the clinical findings, with elevated levels of creatinine, creatine phosphokinase, and CRP. Discussion. We would like to pinpoint the importance of this complication and our concern of prescribing it for psychiatric patients with chronic somatic comorbidities.

  7. Maintaining remission in ulcerative colitis – role of once daily extended-release mesalamine

    Directory of Open Access Journals (Sweden)

    Lilliana Oliveira

    2011-02-01

    Full Text Available Lilliana Oliveira, Russell D CohenThe Department of Medicine, Section of Gastroenterology, University of Chicago Medical Center, Chicago, IL, USAAbstract: The aminosalicylates (5-ASA; also referred to as mesalamine-based agents are considered as first-line in the maintenance of remission of mild to moderate ulcerative colitis (UC. Traditionally these agents have required a large pill burden and multiple daily dosing regimens which may account for the low adherence rates, especially in patients in remission. Extended-release mesalamine is the first once daily mesalamine product approved by the Food and Drug Administration for the maintenance of UC remission. This review will examine the pharmacokinetics, dosing, efficacy, and safety data of extended-release mesalamine, and discuss the potential role of improving medication compliance and decreasing costs in UC maintenance.Keywords: ulcerative colitis, 5-ASA, mesalamine, adherence, compliance, quality of life, costs

  8. Management of obesity and cardiometabolic risk – role of phentermine/extended release topiramate

    OpenAIRE

    Sweeting AN; Tabet E; Caterson ID; Markovic TP

    2014-01-01

    Arianne N Sweeting,1 Eddy Tabet,1 Ian D Caterson,1,2 Tania P Markovic1,2 1Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 2Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, NSW, Australia Abstract: The US Food and Drug Administration (FDA) recently approved lorcaserin and the combination of phentermine and extended release topiramate (phentermine/topiramate ER) for the treatment of obesity in conjunction with ...

  9. Extended-release morphine sulfate in treatment of severe acute and chronic pain

    OpenAIRE

    Balch, Robert J; Andrea Trescot

    2010-01-01

    Robert J Balch, Andrea TrescotDepartment of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA USAAbstract: Morphine is the archetypal opioid analgesic. Because it is a short-acting opioid, its use has been limited to the management of acute pain. The development of extended-release formulations have resulted in the increased utilization of morphine in chronic pain conditions. This review documents the history of morphine use in pain treatment, and describes the metabolis...

  10. Design and development of bilayer tablet for immediate and extended release of acarbose and metformin HCl

    Directory of Open Access Journals (Sweden)

    Meenakshi Joshi

    2014-01-01

    Full Text Available The present investigation studied a novel Bilayer tablet having extended release (ER system of metformin HCl (M.HCl with Eudragit RS 100 and RL 100 and immediate release (IR system of Acarbose with PVP K30 and PEG 6000 in different ratios using solvent evaporation technique. Solid dispersions (SDs were characterized by Fourier Transform-Infra Red spectroscopy, Diffrential Scanning Calorimetry, X-Ray Diffractometry and Scanning Electron Microscopy. Selected SD system was subjected to Bilayer tablet preparation by direct compression. Compressed tablets were evaluated for physical parameters, drug release and stability. SEM studies suggested the homogenous dispersion of the drug in polymers. FT-IR studies confirmed the formation of hydrogen bonding between the drug and polymer. XRD and DSC suggested the amorphous nature of the drug in SDs. All tablet formulations showed compliance with pharmacopoeial standards. In-vitro dissolution kinetics followed the Higuchi model via a non-fickian diffusion controlled release mechanism after the initial burst release. Stability studies conducted for optimized formulation did not show any change in the physical properties, drug content and drug release. Bilayer tablets showed an IR effect to provide the loading dose of the drug, followed by ER effect for 12 h, indicating a promising potential of the M.HCl and Acarbose Bilayer tablet as an alternative to the conventional dosage form.

  11. Preparation and scale up of extended-release tablets of bromopride

    Directory of Open Access Journals (Sweden)

    Guilherme Neves Ferreira

    2014-04-01

    Full Text Available Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34th edition. DOE studies were conducted using Minitab(tm software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab(tm software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed.

  12. Preparation and characterization of a coacervate extended-release microparticulate delivery system for Lactobacillus rhamnosus

    Directory of Open Access Journals (Sweden)

    Alli SMA

    2011-08-01

    Full Text Available Sk Md Athar Alli Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, IndiaBackground: The purpose of this study was to develop a mucoadhesive coacervate microparticulate system to deliver viable Lactobacillus rhamnosus cells into the gut for an extended period of time while maintaining high numbers of viable cells within the formulation throughout its shelf-life and during gastrointestinal transit.Methods: Core coacervate mucoadhesive microparticles of L. rhamnosus were developed using several grades of hypromellose and were subsequently enteric-coated with hypromellose phthalate. Microparticles were evaluated for percent yield, entrapment efficiency, surface morphology, particle size, size distribution, zeta potential, flow properties, in vitro swelling, mucoadhesion properties, in vitro release profile and release kinetics, in vivo probiotic activity, and stability. The values for the kinetic constant and release exponent of model-dependent approaches, the difference factor, similarity factor, and Rescigno indices of model-independent approaches were determined for analyzing in vitro dissolution profiles.Results: Experimental microparticles of formulation batches were of spherical shape with percent yields of 41.24%–58.18%, entrapment efficiency 45.18%–64.16%, mean particle size 33.10–49.62 µm, and zeta potential around -11.5 mV, confirming adequate stability of L. rhamnosus at room temperature. The in vitro L. rhamnosus release profile follows zero-order kinetics and depends on the grade of hypromellose and the L. rhamnosus to hypromellose ratio.Conclusion: Microparticles delivered L. rhamnosus in simulated intestinal conditions for an extended period, following zero-order kinetics, and exhibited appreciable mucoadhesion in simulated intestinal conditions.Keywords: Lactobacillus rhamnosus, mucoadhesive, microparticles, extended-release, intestine

  13. Combined use of extended-release niacin and atorvastatin: safety and effects on lipid modification

    Institute of Scientific and Technical Information of China (English)

    SANG Zhen-chi; WANG Fei; ZHOU Qing; LI Yue-hua; LI Yi-gang; WANG Hong-ping; CHEN Shu-yan

    2009-01-01

    Background Cholesterol-lowering therapy with statins has been reported to reduce the morbidity and mortality of cardiovascular diseases. This study aimed to investigate the effects of combined application of extended-release niacin and atorvastatin on lipid profile modification and the risks of adverse events in patients with coronary artery disease. Methods Consecutive 108 patients with coronary artery disease and serum total cholesterol (TC) ≥ 3.5 mmol/L were randomized into two groups: group A using atorvastatin and group B using extended-release niacin (niacin ER) and atorvastatin. Plasma lipid profile, glucose, and adverse events were assessed at the hospitalization, and 6 and 12 months after treatment. In addition, clinical cardiovascular events were evaluated after 12 months of treatment. Results The levels of TC, low density lipoprotein cholesterol (LDL-C) were significantly decreased (P0.05). Conclusions Combined use of extended-release niacin with atorvastatin was superior to atorvastatin monotherapyalone in lipid profile regulation. Combination therapy with niacin ER and atorvastatin was well tolerated and safe in patients with coronary artery disease.

  14. Update on prescription extended-release opioids and appropriate patient selection

    Directory of Open Access Journals (Sweden)

    Brennan MJ

    2013-07-01

    Full Text Available Michael J Brennan The Pain Center of Fairfield, Fairfield, CT, USA Abstract: Chronic pain is largely underdiagnosed, often undertreated, and expected to increase as the American population ages. Many patients with chronic pain require long-term treatment with analgesic medications, and pain management may involve use of prescription opioids for patients whose pain is inadequately controlled through other therapies. Yet because of the potential for abuse and addiction, many clinicians hesitate to treat their patients with pain with potentially beneficial agents. Finding the right opioid for the right patient is the first – often complicated – step. Ensuring that patients continue to properly use the medication while achieving therapeutic analgesic effects is the long-term goal. Combined with careful patient selection and ongoing monitoring, new formulations using extended-release technologies incorporating tamper-resistant features may help combat the growing risk of abuse or misuse, which will hopefully reduce individual suffering and the societal burden of chronic pain. The objective of this manuscript is to provide an update on extended-release opioids and to provide clinicians with a greater understanding of which patients might benefit from these new opioid formulations and how to integrate the recommended monitoring for abuse potential into clinical practice. Keywords: chronic pain, opioid analgesics, extended release, abuse prevention

  15. Pharmacokinetic considerations of formulation: extended-release metoprolol succinate in the treatment of heart failure.

    Science.gov (United States)

    Wikstrand, John; Andersson, Bert; Kendall, Martin J; Stanbrook, Hilary; Klibaner, Michael

    2003-02-01

    Extended-release (ER) metoprolol succinate is a controlled-release formulation designed to deliver metoprolol succinate at a near constant rate for approximately 20 h, independent of food intake and gastrointestinal pH. Once-daily dosing of ER metoprolol succinate 12.5-200 mg produces even plasma concentrations over a 24-h period, without the marked peaks and troughs characteristically observed with the immediate-release (IR) formulation. This leads to consistent beta1-blockade over 24 h, while maintaining cardioselectivity at doses up to 200 mg daily. Pharmacokinetic studies have also been performed in heart failure patients and have demonstrated that ER metoprolol succinate is associated with a more pronounced and even beta1-blockade over a 24-h period than the IR formulation. The efficacy and good tolerability of ER metoprolol succinate in heart failure patients has now been demonstrated in a large-scale clinical trial.

  16. Tablet splitting: Product quality assessment of metoprolol succinate extended release tablets.

    Science.gov (United States)

    Zhao, Na; Zidan, Ahmed; Tawakkul, Mobin; Sayeed, Vilayat A; Khan, Mansoor

    2010-11-30

    Metoprolol succinate extended release tablets comprise a multiple unit system containing metoprolol succinate in a multitude of controlled release pellets. Each pellet acts as a separate drug delivery unit and is designed to deliver metoprolol continuously over the dosage interval. Despite the flexibility that controlled release pellets may offer, segregation is one of the challenges that commonly occur during tableting for such drug delivery system. Since all commercial metoprolol succinate extended release tablets are scored, they are deemed suitable for splitting. The present study was aimed at utilizing an innovative technology to determine the dose uniformity for split tablets. Four marketed drug products consisting of innovator and generics were evaluated for effect of splitting on weight, assay and content uniformity. Novel analytical tool such as near infrared (NIR) chemical imaging was used to visualize the distribution of metoprolol succinate and functional excipients on the surfaces of the marketed tablets. The non-homogeneous distribution of directly compressed metoprolol succinate beads on the surface of the tablets as well as the split intersection explained the large variation in the split tablets' weight and content uniformity results. The obtained results indicated the usefulness of NIR chemical imaging to determine the need for content uniformity studies for certain split tablets.

  17. Safety and efficacy considerations due to misuse of extended-release formulations of stimulant medications.

    Science.gov (United States)

    Jain, Rakesh; Stark, Jeffrey G

    2016-09-01

    Amphetamine or methylphenidate are first-line options for treating attention-deficit/hyperactivity disorder (ADHD). Deviations from suggested routes of administration such as crushing, chewing, intravenous administration, or snorting stimulant medication may alter the release rate, absorption, and bioavailability of the active drug. Additionally, the pharmacokinetic (PK) profiles of extended-release formulations of certain medications (e.g., some opioids) are known to be dangerously altered when consumed with alcohol; specifically, there is an unintended, rapid release of a significant portion of the drug (dose dumping). In vitro data suggest some extended-release stimulants dose dump in the presence of alcohol, which is of concern because the ADHD patient population is at risk for alcohol abuse. This article reviews the available scientific literature concerning modifications to routes of administration that may alter PK properties of stimulant-based medication for treating ADHD. These modifications are of clinical interest because they may pose safety hazards and affect efficacy. Electronic databases were searched for appropriate studies using relevant search terms. The misuse and abuse potential for stimulants and the efforts to prevent misuse are also discussed. Future research should be focused on determining the PK ramifications of stimulant misuse, along with developing new formulations with abuse-deterrent properties.

  18. Pharmacokinetics study of extended release formulations of buspirone hydrochloride in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    CUI Meng-cun; LI Jing-lai; CHEN Yan; WANG Xiao-ying; QIAO Jian-zhong; ZHANG Zhen-qing; RUAN Jin-xiu

    2008-01-01

    Objective To evaluate the pharmacokinetics (PK) properties of extended release formulations of buspirone hydrochloride in Beagle dogs. Methods A randomized, two period, two treatment, two sequence crossover bioequivalenee study was designed; six healthy Beagle dogs were randomly divided into two groups, each group was orally given buspirone tablets or buspirone extended capsule containing 15 mg buspirone hydrochloride. Blood samples (about 1 mL) were collected in heparinized tubes before dosing and at 0.33, 0.67, 1,2, 3, 4, 6, 8, 10, 12, 18, 24 h after administration, and were then immediately centrifuged at 3000 rpm for 15 min. The pharmacokinetics (PK) properties of the drugs were evaluated using the liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method. Results The mean tmax was 4.7, 0.8 h and Cmax values was 1.8, 6.9 μg·L-1, respectively for the sustained-release test (capsule) and reference formulation (tablet). When compared to the tablets, the residence time of the sustained capsules was dramatically prolonged and Cmax Was reduced (P<0.01). The initial release speed was slow and stable. The bioavailability was similar to the common tablets. Conclusions The sustained capsule had showed good pharmacokinetics property of sustained-release in the Beagle dogs.

  19. Extended release matrix tablets of Stavudine: Formulation and in vitro evaluation

    Directory of Open Access Journals (Sweden)

    Saravanakumar M

    2010-01-01

    Full Text Available During the past two decades, there has been a steady increase in both the number of antiretroviral medications and the number of possible regimens available to manage human immunodeficiency virus (HIV and acquired immune deficiency syndrome (AIDS. But still, regimen fails due to some reasons such as toxicity, adverse effects, and consequent difficulties with patient adherence. Stavudine is the Food and Drug Administration approved drug for clinical use for the treatment of HIV infection, AIDS, and AIDS related conditions, either alone or in combination with other antiviral agents. The side effects of Stavudine are dose dependent and a reduction of the total administered dose reduces the severity of the toxicity. To reduce the frequency of administration and to improve patient compliance, a once daily sustained release formulation of Stavudine is desirable. Hence, in the present work, an attempt has been made to develop once daily sustained release matrix tablets of Stavudine using putative hydrophilic matrix materials such as hydroxyl propyl methyl cellulose (HPMC K4M and Carbopol 974P. The prepared extended release tablets were then evaluated for various physical tests like diameter, thickness, weight variation, hardness, friability, and drug content uniformity. The results of all these tests were found to be satisfactory. Formulation F9 extended the drug release till the end of 24 hours and showed higher r values for zero order plot, indicating that drug release followed zero order kinetics. This finding reveals that above a particular concentration, HPMC K4M and Carbopol 974P are capable of providing almost zero order drug release.

  20. Evaluation of the tamper-resistant properties of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets.

    Science.gov (United States)

    Eisenhauer, Tiffani D; Matchett, Mike; Heasley, Ralph; Morton, Terri; Devarakonda, Krishna; Giuliani, Michael; Young, Jim L; Barrett, Thomas

    2016-01-01

    Abuse potential of extended-release (ER) opioid tablets increases if tampering causes rapid opioid release. To evaluate the susceptibility to tampering of biphasic immediate-release (IR)/ER oxycodone (OC)/acetaminophen (APAP) tablets compared with IR OC/APAP tablets. IR/ER OC/APAP and IR OC/APAP tablets were tested at room temperature and after heating, freezing and microwaving. Resistance to crushing was tested using manual and powered tools (e.g. spoons, mortar and pestle, blender, coffee grinder). Tampered tablets were tested for suitability for snorting, OC extraction in solvents and ease of drawing into a syringe. Dissolution of IR/ER OC/APAP in gastric fluid with and without ethanol was tested to determine the potential for facilitating precipitous release of opioid from the tablet. IR/ER OC/APAP tablets were more crush resistant than IR OC/APAP tablets. Heating, freezing and microwaving had no effect on crush resistance of IR/ER OC/APAP tablets. Although a mortar and pestle pulverized IR/ER OC/APAP tablets, upon contact with solvent, the powder formed a thick gel judged unsuitable for absorption through the nasal mucosa and could not be drawn into a syringe. In contrast, powder from crushed IR OC/APAP tablets dissolved readily, was judged suitable for snorting, and was easily drawn into a syringe. Dissolution of IR/ER OC/APAP tablets in gastric fluid was slowed by the addition of ethanol. IR/ER OC/APAP tablets are resistant to crushing and dissolution compared with IR OC/APAP tablets. IR/ER OC/APAP tablets may have less potential for abuse involving tampering compared with IR OC/APAP tablets.

  1. Clinical Efficacy of Fluvoxamine and Functional Polymorphism in a Serotonin Transporter Gene on Childhood Autism

    Science.gov (United States)

    Sugie, Yoko; Sugie, Hideo; Fukuda,Tokiko; Ito, Masataka; Sasada, Yumiko; Nakabayashi, Mutsumi; Fukashiro, Kazunobu; Ohzeki, Takehiko

    2005-01-01

    We studied the correlation between response to fluvoxamine and serotonin transporter gene promoter region polymorphism (5-HTTLPR). Eighteen children with autistic disorder completed a 12-week double-blind, placebo-controlled, randomized crossover study of fluvoxamine. Behavioral assessments were obtained before and at 12 weeks of treatment.…

  2. Monolithic LC method applied to fesoterodine fumarate low dose extended-release tablets: Dissolution and release kinetics

    Directory of Open Access Journals (Sweden)

    Maximiliano S. Sangoi

    2015-04-01

    Full Text Available A dissolution test for fesoterodine low dose extended-release tablets using liquid chromatographic (LC method equipped with a C18 monolithic column was developed and validated. LC system was operated isocratically at controlled temperature (40 °C using a mobile phase of acetonitrile:methanol:0.03 M ammonium acetate (pH 3.8 (30:15:55, v/v/v, run at a flow rate of 1.5 mL/min and detected at 208 nm. The best dissolution conditions for this formulation were achieved using a USP apparatus 2 (paddle at 100 rpm and 900 mL of phosphate buffer at pH 6.8 as the dissolution medium. Validation parameters such as the specificity, linearity, accuracy, precision, and robustness were evaluated according to international guidelines, giving results within the acceptable range. The kinetic parameters of drug release were also investigated using model-dependent methods and the dissolution profiles were best described by the Higuchi model. The validated dissolution test can be applied for quality control of this formulation.

  3. Monolithic LC method applied to fesoterodine fumarate low dose extended-release tablets:Dissolution and release kinetics

    Institute of Scientific and Technical Information of China (English)

    Maximiliano S. Sangoi; Vítor Todeschini; Martin Steppe

    2015-01-01

    A dissolution test for fesoterodine low dose extended-release tablets using liquid chromato-graphic (LC) method equipped with a C18 monolithic column was developed and validated. LC system was operated isocratically at controlled temperature (40 1C) using a mobile phase of acetonitrile:methanol:0.03 M ammonium acetate (pH 3.8) (30:15:55, v/v/v), run at a flow rate of 1.5 mL/min and detected at 208 nm. The best dissolution conditions for this formulation were achieved using a USP apparatus 2 (paddle) at 100 rpm and 900 mL of phosphate buffer at pH 6.8 as the dissolution medium. Validation parameters such as the specificity, linearity, accuracy, precision, and robustness were evaluated according to international guidelines, giving results within the acceptable range. The kinetic parameters of drug release were also investigated using model-dependent methods and the dissolution profiles were best described by the Higuchi model. The validated dissolution test can be applied for quality control of this formulation.

  4. Tapentadol extended-release for treatment of chronic pain: a review

    Directory of Open Access Journals (Sweden)

    Vadivelu N

    2011-08-01

    Full Text Available Nalini Vadivelu1, Alexander Timchenko1, Yili Huang2, Raymond Sinatra11Department of Anesthesiology, Yale University School of Medicine, New Haven, CT; 2Internal Medicine, North Shore-LIJ Plainview Hospital, Plainview, NY, USAAbstract: Tapentadol is a centrally acting analgesic with a dual mechanism of action of mu receptor agonism and norepinephrine reuptake inhibition. Tapentadol immediate-release is approved by the US Food and Drug Administration for the management of moderate-to-severe acute pain. It was developed to decrease the intolerability issue associated with opioids. Tapentadol extended-release has a 12-hour duration of effect, and has recently been evaluated for pain in patients with chronic osteoarthritis, low back pain, and pain associated with diabetic peripheral neuropathy. Tapentadol extended-release was found to provide safe and highly effective analgesia for the treatment of chronic pain conditions, including moderate-to-severe chronic osteoarthritis pain and low back pain. Initial trials demonstrating efficacy in neuropathic pain suggest that tapentadol has comparable analgesic effectiveness and better gastrointestinal tolerability than opioid comparators, and demonstrates effectiveness in settings of inflammatory, somatic, and neuropathic pain. Gastrointestinal intolerance and central nervous system effects were the major adverse events noted. Tapentadol will need to be rigorously tested in chronic neuropathic pain, cancer-related pain, and cancer-related neuropathic pain.Keywords: osteoarthritis, neuropathic pain, analgesic, opioids, norepinephrine

  5. Profile of extended-release oxycodone/acetaminophen for acute pain

    Directory of Open Access Journals (Sweden)

    Bekhit MH

    2015-10-01

    Full Text Available Mary Hanna Bekhit1–51David Geffen School of Medicine, 2Ronald Reagan UCLA Medical Center, 3UCLA Ambulatory Surgery Center, 4UCLA Wasserman Eye Institute, 5UCLA Martin Luther King Community Hospital, University of California Los Angeles, Los Angeles, CA, USA Abstract: This article provides a historical and pharmacological overview of a new opioid analgesic that boasts an extended-release (ER formulation designed to provide both immediate and prolonged analgesia for up to 12 hours in patients who are experiencing acute pain. This novel medication, ER oxycodone/acetaminophen, competes with current US Food and Drug Administration (FDA-approved opioid formulations available on the market in that it offers two benefits concurrently: a prolonged duration of action, and multimodal analgesia through a combination of an opioid (oxycodone with a nonopioid component. Current FDA-approved combination analgesics, such as Percocet (oxycodone/acetaminophen, are available solely in immediate-release (IR formulations. Keywords: opioid, analgesic, xartemis, acute postsurgical pain, substance abuse, acetaminophen, extended release 

  6. Risk based in vitro performance assessment of extended release abuse deterrent formulations.

    Science.gov (United States)

    Xu, Xiaoming; Gupta, Abhay; Al-Ghabeish, Manar; Calderon, Silvia N; Khan, Mansoor A

    2016-03-16

    High strength extended release opioid products, which are indispensable tools in the management of pain, are associated with serious risks of unintentional and potentially fatal overdose, as well as of misuse and abuse that might lead to addiction. The issue of drug abuse becomes increasingly prominent when the dosage forms can be readily manipulated to release a high amount of opioid or to extract the drug in certain products or solvents. One approach to deter opioid drug abuse is by providing novel abuse deterrent formulations (ADF), with properties that may be viewed as barriers to abuse of the product. However, unlike regular extended release formulations, assessment of ADF technologies are challenging, in part due to the great variety of formulation designs available to achieve deterrence of abuse by oral, parenteral, nasal and respiratory routes. With limited prior history or literature information, and lack of compendial standards, evaluation and regulatory approval of these novel drug products become increasingly difficult. The present article describes a risk-based standardized in-vitro approach that can be utilized in general evaluation of abuse deterrent features for all ADF products.

  7. Topiramate Extended-Release Options: A Focus on Efficacy and Safety in Epilepsy and Comorbidities

    Directory of Open Access Journals (Sweden)

    Yuchen Wang

    2017-02-01

    Full Text Available Topiramate (TPM is effective for multiple seizure types and epilepsy syndromes in children and adults. Topiramate has adverse effects (including cognitive, depression, renal stones, but many of these are low incidence when started at a low dose and slowly titrated to 100 to 200 mg/day. Also, TPM has proven benefit for migraine, obesity, eating disorders, and alcohol use disorders, which can be comorbid in patients with epilepsy and may also be effective in subpopulations within specific psychiatric diagnoses. Recently approved extended-release formulations of TPM (Trokendi and Qudexy in the United States have reliable data supporting their safety and efficacy for patients with epilepsy. They have potential for more rapid titration within 1 month to 200 mg/day and have better patient retention than TPM immediate-release, but there are no robust double-blind randomized controlled trials comparing the different formulations. We expect the once per day extended-release formulations to improve medication adherence compared with the twice per day formulations. This has significant potential to improve outcomes in epilepsy and the other TPM-responsive disorders.

  8. Identification of critical formulation and processing variables for metoprolol tartrate extended-release (ER) matrix tablets.

    Science.gov (United States)

    Rekhi, G S; Nellore, R V; Hussain, A S; Tillman, L G; Malinowski, H J; Augsburger, L L

    1999-06-02

    The objective of this study, was to examine the influence of critical formulation and processing variables as described in the AAPS/FDA Workshop II report on scale-up of oral extended-release dosage forms, using a hydrophilic polymer hydroxypropyl methylcellulose (Methocel K100LV). A face-centered central composite design (26 runs+3 center points) was selected and the variables studied were: filler ratio (lactose:dicalcium phosphate (50:50)), polymer level (15/32.5/50%), magnesium stearate level (1/1.5/2%), lubricant blend time (2/6/10 min) and compression force (400/600/800 kg). Granulations (1.5 kg, 3000 units) were manufactured using a fluid-bed process, lubricated and tablets (100 mg metoprolol tartrate) were compressed on an instrumented Manesty D3B rotary tablet press. Dissolution tests were performed using USP apparatus 2, at 50 rpm in 900 ml phosphate buffer (pH 6.8). Responses studied included percent drug released at Q1 (1 h), Q4, Q6, Q12. Analysis of variance indicated that change in polymer level was the most significant factor affecting drug release. Increase in dicalcium phosphate level and compression force were found to affect the percent released at the later dissolution time points. Some interaction effects between the variables studied were also found to be statistically significant. The drug release mechanism was predominantly found to be Fickian diffusion controlled (n=0.46-0.59). Response surface plots and regression models were developed which adequately described the experimental space. Three formulations having slow-, medium- and fast-releasing dissolution profiles were identified for a future bioavailability/bioequivalency study. The results of this study provided the framework for further work involving both in vivo studies and scale-up.

  9. Metformin extended release for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Schwartz, Sherwyn L; Wu, Jacqueline F; Berner, Bret

    2006-04-01

    Metformin extended release (ER) (Glumetza, Depomed, Inc.) is a recently approved formulation that provides effective and well-tolerated glycaemic control with once-daily dosing. Metformin ER has similar bioavailability to conventional immediate-release (IR) formulations. In controlled clinical trials, metformin ER provided effective glycaemic control for 24 weeks when administered either as monotherapy or in combination with sulfonylurea. Good glycaemic control was maintained for an additional 24 weeks during an open-label extension study. Once-daily dosing with metformin ER 1500 mg/day was as effective as twice-daily dosing with metformin IR at the same total daily dose. Metformin ER was well tolerated at doses of 1500 or 2000 mg/day, with no increase in the frequency or severity of adverse events at the higher dose.

  10. Effects of Extended-Release Nicotinic Acid on Apolipoprotein (a) Kinetics in Hypertriglyceridemic Patients.

    Science.gov (United States)

    Croyal, Mikaël; Ouguerram, Khadija; Passard, Maxime; Ferchaud-Roucher, Véronique; Chétiveaux, Maud; Billon-Crossouard, Stéphanie; de Gouville, Anne-Charlotte; Lambert, Gilles; Krempf, Michel; Nobécourt, Estelle

    2015-09-01

    To determine the mechanisms by which extended-release nicotinic acid reduces circulating lipoprotein (a) concentrations in hypertriglyceridemic patients. Eight nondiabetic, obese male subjects (aged 48±12 years; body mass index, 31.2±1.8 kg/m(2)) with hypertriglyceridemia (triglycerides, 226±78 mg/dL) were enrolled in an 8 week, double blind, placebo-controlled cross-over study. At the end of each treatment phase, fasted subjects received a 10 µmol/L per kg bolus injection of [5,5,5-(2)H3]-l-Leucine immediately followed by constant infusion of [5,5,5-(2)H3]-l-Leucine (10 µmol L(-1) kg(-1) h(-1)) for 14 hours, and blood samples were collected. A liquid chromatography-tandem mass spectrometry method was used to study apolipoprotein (a) (Apo(a)) kinetics. The fractional catabolic rate of Apo(a) was calculated with a single compartmental model using the apolipoprotein B100 (ApoB100) containing very low density lipoprotein tracer enrichment as a precursor pool. Extended-release nicotinic acid decreased plasma triglycerides (-46%; P=0.023), raised high-density lipoprotein cholesterol (+20%; P=0.008), and decreased Apo(a) plasma concentrations (-20%; P=0.008). Extended-release nicotinic acid also decreased ApoB100 (22%; P=0.008) and proprotein convertase subtilisin/kexin type 9 (PCSK9, -29%; P=0.008) plasma concentrations. Apo(a) fractional catabolic rate and production rates were decreased by 37% (0.58±0.28 versus 0.36±0.19 pool/d; P=0.008) and 50% (1.4±0.8 versus 0.7±0.4 nmol/kg per day; P=0.008), respectively. Extended-release nicotinic acid treatment decreased Apo(a) plasma concentrations by 20%, production rates by 50%, and catabolism by 37%. ApoB100 and PCSK9 concentrations were also decreased by treatment, but no correlation was found with Apo(a) kinetic parameters. © 2015 American Heart Association, Inc.

  11. Glaucoma therapy by extended release of timolol from nanoparticle loaded silicone-hydrogel contact lenses.

    Science.gov (United States)

    Jung, Hyun Jung; Abou-Jaoude, Michelle; Carbia, Blanca E; Plummer, Caryn; Chauhan, Anuj

    2013-01-10

    Glaucoma is the second major cause of blindness in the world after cataract. Glaucoma management through eye drops that reduce the intraocular pressure (IOP) has major deficiencies including low patient compliance and low bioavailability. Extended wear contact lenses that deliver glaucoma drugs for extended periods could increase patient compliance, while also increasing the bioavailability. To develop extended wear contact lenses that can also provide extended glaucoma therapy, we disperse nanoparticles of PGT (propoxylated glyceryl triacylate) that contain a glaucoma drug timolol. The particles can also be loaded into prefabricated lenses by soaking the lenses in a solution of particles in ethanol. The particle loaded gels can release timolol in phosphate buffered saline (PBS) for about a month at room temperature. The most likely rate controlling mechanism is hydrolysis of the ester bond that links timolol to the PGT matrix, but other mechanisms such as water and drug diffusion, drug dissolution, drug-polymer chain cleavage, time-dependent drug permeability within the polymeric matrix, etc. may also be important. Nanoparticle incorporation in the silicone hydrogels results in reduction in ion and oxygen permeabilities, and an increase in modulus, and the impact on each of these properties is proportional to the particle loading. A gel with 5% particle loading can deliver timolol at therapeutic doses for about a month at room temperature, with a minimal impact on critical lens properties. Preliminary animal studies in Beagle dogs conducted with lenses in which particles are loaded by soaking the lenses in ethanol show a reduction in IOP.

  12. Effect of combination of acrylic polymers on the release of nevirapine formulated as extended release matrix pellets using extrusion and spheronization technique.

    Science.gov (United States)

    Sharma, Anshuli; Prasad, Anjaneya; Dua, Kamal; Singh, Gurvinder

    2014-01-01

    The aim of the present research work was to formulate and evaluate the extended release matrix pellets of nevirapine using extrusion and spheronization technique which will be an alternative technique for making extended release dosage forms and to compare the drug release profiles of the formulations with the reference product. In vitro dissolutions were carried out in 0.04M Phosphate buffer pH 6.8 with 2% w/v SLS (sodium lauryl sulphate) for 24 hours with USP type I apparatus at 75rpm. The drug release from the optimised formulation was comparable to that of the reference product and follows first order kinetics followed by non-fickian transport mechanism of drug release which confirms the drug release pattern involves complex mixture of diffusion and erosion. The similarity factor, f2 value of optimised formulation was found to be 70, which shows that the developed formulation was comparable to that of the reference product.

  13. Extended-release naltrexone reduces alcohol consumption among released prisoners with HIV disease as they transition to the community.

    Science.gov (United States)

    Springer, Sandra A; Di Paola, Angela; Azar, Marwan M; Barbour, Russell; Krishnan, Archana; Altice, Frederick L

    2017-05-01

    Alcohol use disorders (AUDs) are highly prevalent among persons living with HIV (PLH) within the criminal justice system (CJS). Extended-release naltrexone (XR-NTX) has not been previously evaluated among CJS-involved PLH with AUDs. A randomized, double-blind, placebo-controlled trial was conducted among 100 HIV+ prisoners with AUDs. Participants were randomized 2:1 to receive 6 monthly injections of XR-NTX or placebo starting one week prior to release. Using multiple imputation strategies for data missing completely at random, data were analyzed for the 6-month post-incarceration period. Main outcomes included: time to first heavy drinking day; number of standardized drinks/drinking day; percent of heavy drinking days; pre- to post-incarceration change in average drinks/day; total number of drinking days; and a composite alcohol improvement score comprised of all 5 parameters. There was no statistically significant difference overall between treatment arms for time-to-heavy-drinking day. However, participants aged 20-29 years who received XR-NTX had a longer time to first heavy drinking day compared to the placebo group (24.1 vs. 9.5days; p<0.001). There were no statistically significant differences between groups for other individual drinking outcomes. A sub-analysis, however, found participants who received ≥4 XR-NTX were more likely (p<0.005) to have improved composite alcohol scores than the placebo group. Post-hoc power analysis revealed that despite the study being powered for HIV outcomes, sufficient power (0.94) was available to distinguish the observed differences. Among CJS-involved PLH with AUDs transitioning to the community, XR-NTX lengthens the time to heavy drinking day for younger persons; reduces alcohol consumption when using a composite alcohol consumption score; and is not associated with any serious adverse events. Published by Elsevier B.V.

  14. Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms.

    Science.gov (United States)

    Lin, Zhongqiang; Zhou, Deliang; Hoag, Stephen; Qiu, Yihong

    2016-03-01

    Bioequivalence (BE) studies are often required to ensure therapeutic equivalence for major product and manufacturing changes. Waiver of a BE study (biowaiver) is highly desired for such changes. Current regulatory guidelines allow for biowaiver of proportionally similar lower strengths of an extended release (ER) product provided it exhibits similar dissolution to the higher strength in multimedia. The objective of this study is to demonstrate that (1) proportionally similar strengths of ER tablets exhibiting similar in vitro dissolution profiles do not always assure BE and (2) different strengths that do not meet the criteria for dissolution profile similarity may still be bioequivalent. Four marketed ER tablets were used as model drug products. Higher and lower (half) strength tablets were prepared or obtained from commercial source. In vitro drug release was compared using multi-pH media (pH 1.2, 4.5, 6.8) per regulatory guidance. In vivo performance was assessed based on the available in vivo BE data or established in vitro-in vivo relationships. This study demonstrated that the relationship between in vitro dissolution and in vivo performance is complex and dependent on the characteristics of specific drug molecules, product design, and in vitro test conditions. As a result, proportionally similar strengths of ER dosage forms that meet biowaiver requirements per current regulatory guidelines cannot ensure bioequivalence in all cases. Thus, without an established relationship between in vitro and in vivo performance, granting biowaiver based on passing in vitro tests may result in the approval of certain bioinequivalent products, presenting risks to patients. To justify any biowaiver using in vitro test, it is essential to understand the effects of drug properties, formulation design, product characteristics, test method, and its in vivo relevance. Therefore, biowaiver requirements of different strengths of ER dosage forms specified in the current regulatory

  15. Investigation into the Effect of Ethylcellulose Viscosity Variation on the Drug Release of Metoprolol Tartrate and Acetaminophen Extended Release Multiparticulates-Part I.

    Science.gov (United States)

    Mehta, R; Teckoe, J; Schoener, C; Workentine, S; Ferrizzi, D; Rajabi-Siahboomi, A

    2016-12-01

    Ethylcellulose is one of the most commonly used polymers to develop reservoir type extended release multiparticulate dosage forms. For multiparticulate extended release dosage forms, the drug release is typically governed by the properties of the barrier membrane coating. The ICH Pharmaceutical Development Guideline (ICH Q8) requires an understanding of the influence of critical material attributes and critical process parameters on the drug release of a pharmaceutical product. Using this understanding, it is possible to develop robust formulations with consistent drug release characteristics. Critical material attributes for ethylcellulose were evaluated, and polymer molecular weight variation (viscosity) was considered to be the most critical attribute that can impact drug release. To investigate the effect of viscosity variation within the manufacturer's specifications of ethylcellulose, extended release multiparticulate formulations of two model drugs, metoprolol tartrate and acetaminophen, were developed using ETHOCEL™ as the rate controlling polymer. Quality by Design (QbD) samples of ETHOCEL Std. 10, 20, and 100 Premium grades representing the low, medium, and high molecular weight (viscosity) material were organically coated onto drug layered multiparticulates to a 15% weight gain (WG). The drug release was found to be similar (f 2 > 50) for both metoprolol tartrate and acetaminophen multiparticulates at different coating weight gains of ethylcellulose, highlighting consistent and robust drug release performance. The use of ETHOCEL QbD samples also serves as a means to develop multiparticulate dosage formulations according to regulatory guidelines.

  16. Effects of extended-release niacin with laropiprant in high-risk patients

    DEFF Research Database (Denmark)

    Landray, Martin J; Haynes, Richard; Hopewell, Jemma C

    2014-01-01

    BACKGROUND: Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein (HDL) choleste......BACKGROUND: Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein (HDL......) cholesterol level, but its clinical efficacy and safety are uncertain. METHODS: After a prerandomization run-in phase to standardize the background statin-based LDL cholesterol-lowering therapy and to establish participants' ability to take extended-release niacin without clinically significant adverse...... effects, we randomly assigned 25,673 adults with vascular disease to receive 2 g of extended-release niacin and 40 mg of laropiprant or a matching placebo daily. The primary outcome was the first major vascular event (nonfatal myocardial infarction, death from coronary causes, stroke, or arterial...

  17. Management of obesity and cardiometabolic risk – role of phentermine/extended release topiramate

    Directory of Open Access Journals (Sweden)

    Sweeting AN

    2014-02-01

    Full Text Available Arianne N Sweeting,1 Eddy Tabet,1 Ian D Caterson,1,2 Tania P Markovic1,2 1Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 2Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, NSW, Australia Abstract: The US Food and Drug Administration (FDA recently approved lorcaserin and the combination of phentermine and extended release topiramate (phentermine/topiramate ER for the treatment of obesity in conjunction with a lifestyle intervention, expanding the therapeutic options for long-term obesity pharmacotherapy, which was previously limited to orlistat. Combination phentermine/topiramate ER is associated with greater weight loss compared to its constituent monotherapy, with a more favorable adverse effect profile. Phentermine/topiramate ER also appears to have beneficial effects on cardiometabolic risk, although longer-term cardiovascular safety data are required. While there are no head-to-head studies among the currently available obesity pharmacotherapy agents, phentermine/topiramate ER appears to have a superior weight loss profile. This review will discuss the epidemiology, natural history, and cardiometabolic risk associated with obesity, provide an overview on current obesity pharmacotherapy, and summarize the recent clinical efficacy and safety data underpinning the FDA's approval of both phentermine/topiramate ER and lorcaserin as pharmacotherapy for a long-term obesity intervention. Keywords: obesity, phentermine/topiramate extended release, safety and efficacy, review

  18. Update on prescription extended-release opioids and appropriate patient selection

    Science.gov (United States)

    Brennan, Michael J

    2013-01-01

    Chronic pain is largely underdiagnosed, often undertreated, and expected to increase as the American population ages. Many patients with chronic pain require long-term treatment with analgesic medications, and pain management may involve use of prescription opioids for patients whose pain is inadequately controlled through other therapies. Yet because of the potential for abuse and addiction, many clinicians hesitate to treat their patients with pain with potentially beneficial agents. Finding the right opioid for the right patient is the first – often complicated – step. Ensuring that patients continue to properly use the medication while achieving therapeutic analgesic effects is the long-term goal. Combined with careful patient selection and ongoing monitoring, new formulations using extended-release technologies incorporating tamper-resistant features may help combat the growing risk of abuse or misuse, which will hopefully reduce individual suffering and the societal burden of chronic pain. The objective of this manuscript is to provide an update on extended-release opioids and to provide clinicians with a greater understanding of which patients might benefit from these new opioid formulations and how to integrate the recommended monitoring for abuse potential into clinical practice. PMID:23900563

  19. Development of a new single dose extended release formulation of cefpodoxime proxetil

    Institute of Scientific and Technical Information of China (English)

    Deepa Karthikeyan; Karthikeyan M

    2010-01-01

    Objective:To develop floating microspheres of cefpodoxime proxetil (CP) in order to achieve an extended retention in the upper GIT for 12 hour.Methods: The microspheres were prepared by non aqueous solvent evaporation method using different ratios of cefpodoxime proxetil, hydroxyl propyl methyl cellulose (HPMC K4M ) and ethyl cellulose (1:1:1, 1:1:2, 1:1:3, 1:1:4, 1:1:5 & 1:1:6), in the mixture of dichloromethane and ethanol at ratio of (1:1),with tween80 as the surfactant.Results: The floating microspheres was extended over 10-12 hours and were characterized by particle size analysis (75-600毺m), buoyancy percentage (68.1%-85.4%), drug entrapment efficiency (67.5%-88.8%), % yield (50.50%-77.31%) andin vitro drug release was studied for 12 hours.Conclusions: The floating microspheres show better result and it may be use full for prolong the drug release in stomach and improve the bioavailability.

  20. Update on extended release quetiapine fumarate in schizophrenia and bipolar disorders

    Directory of Open Access Journals (Sweden)

    El-Khalili N

    2012-11-01

    Full Text Available Nizar El-KhaliliAlpine Clinic, Lafayette, IN, USAAbstract: The atypical antipsychotic quetiapine fumarate is available both as an immediate release (IR and as an extended release (XR formulation allowing flexibility of dosing for individual patients. Approved uses of quetiapine XR include the treatment of schizophrenia (including maintenance therapy for prevention of relapse, the treatment of bipolar disorder (manic and depressive episodes, and the prevention of recurrence in patients with bipolar disorder who respond to quetiapine XR. This narrative review provides an update on quetiapine XR in these indications. The pharmacological profile of quetiapine, including a moderate affinity for dopamine D2 receptors and higher affinity for serotonin 5-hydroxytryptophan (5-HT2A receptors, may explain its broad efficacy and low propensity for extrapyramidal symptoms (EPS. The XR formulation has similar bioavailability but prolonged plasma levels compared with the IR formulation, allowing for less frequent (once-daily dosing. Clinical studies have confirmed the efficacy of quetiapine XR in relieving the acute symptoms of schizophrenia during short-term trials, and reducing the risk for relapse in long-term studies. Direct switching from the IR formulation to the same dose of the XR formulation did not reveal any loss of efficacy or tolerability issues, and switching patients to quetiapine XR from conventional or other atypical antipsychotics (for reasons of insufficient efficacy or tolerability also proved to be beneficial and generally well tolerated. In bipolar disorder, quetiapine XR has also proven effective in relieving acute depressive and manic symptoms. Adverse events with quetiapine XR in patients with either schizophrenia or bipolar disorder are similar to those associated with the IR formulation, the most common being sedation, dry mouth, somnolence, dizziness, and headache. The low propensity for EPS is maintained with the XR formulation

  1. Application of percolation theory in the study of an extended release Verapamil hydrochloride formulation.

    Science.gov (United States)

    Gonçalves-Araújo, Tamara; Rajabi-Siahboomi, Ali R; Caraballo, Isidoro

    2008-09-01

    The percolation theory studies the critical points or percolation thresholds of the system, where one component of the system undergoes a geometrical phase transition, starting to connect the whole system. The objective of the present paper was to study the existence of critical points governing the water and drug transport inside hydroxypropylmethylcellulose (HPMC) hydrophilic matrix systems obtained with different polymer viscosity grades. For this purpose, extended release formulations of Verapamil HCl, have been prepared and studied. The percolation theory has been applied for the first time to multi-component hydrophilic matrices. The materials used to prepare the tablets were Verapamil HCl, four different viscosity grades of HPMC, microcrystalline cellulose, lactose, magnesium stearate and colloidal silicon dioxide NF. In order to estimate the percolation threshold, the behaviour of the kinetic parameters with respect to the volumetric fraction of each component at time zero, was studied. From the point of view of the percolation theory, the optimum concentration for all the studied polymers, to obtain a hydrophilic matrix system for the controlled release of Verapamil HCl is higher than 20% (v/v) HPMC. Above 20% (v/v) HPMC, an infinite cluster of excipient would be formed, ensuring uniform hydration, maintaining integrity of the system and controlling the drug release.

  2. Role and clinical utility of pramipexole extended release in the treatment of early Parkinson's disease.

    Science.gov (United States)

    Hametner, Eva-Maria; Seppi, Klaus; Poewe, Werner

    2012-01-01

    The aim of this article is to provide a short review of the most relevant pharmacological and clinical data on pramipexole extended release (ER) as well as to address the clinical utility and potential advantages of a once-daily formulation especially in the treatment of early Parkinson's disease (PD). Pramipexole is widely established as a symptomatic treatment in early as well as advanced PD. The development of an ER formulation, with stable pramipexole plasma concentration over 24 hours, now offers a bioequivalent once-daily alternative. Double-blind randomized controlled trials in early and advanced PD, have established noninferiority of pramipexole ER compared with immediate release as well as superiority of both formulations over placebo. The overnight switch from the standard to the once-daily formulation was shown to be successful in >80% of patients without requiring any dose adjustments. Potential benefits of the prolonged-release design, which have not yet been formally demonstrated in the pivotal trial program, include improved compliance and a potential for better symptomatic control, particularly in patients with early disease that can be managed with monotherapy.

  3. USE OF EXTENDED-RELEASE PRAMIPEXOLE IN EARLY-STAGE PARKINSON’S DISEASE: DESCRIPTION OF A CLINICAL CASE

    Directory of Open Access Journals (Sweden)

    N. V. Fedorova

    2014-11-01

    Full Text Available The paper considers a clinical case of early-stage mixed Parkinson’s disease (PD with significant affective disorders and restless legs syndrome. Once-daily extended-release pramipexole 3 mg significantly improved a patient’s status and led to regression of movement and affective disorders. The paper gives data on the efficacy of dopamine receptor agonists in treating PD and the benefits of their extended-release formulations.

  4. [Fluvoxamine, amitriptyline and transcranial electrostimulation of the brain in the treatment of chronic daily headache].

    Science.gov (United States)

    Tarasova, S V; Amelin, A V; Skoromets, A A

    2008-01-01

    Efficacy of antidepressants fluvoxamine, amitriptyline and transcranial electrostimulation of the brain in the treatment of chronic daily headache has been studied. Amitriptyline had the highest effect in dosage 50 mg daily but was not well tolerated by patients that resulted in that only 50% of them finished the study. Fluvoxamine had high efficacy and good tolerability in the treatment of chronic daily headache and medication overuse headache. Small dosages of amitriptyline and fluvoxamine potentiated the analgesic effect of transcranial electrostimulation of the brain. The combination of antidepressants with transcranial electrostimulation of the brain alleviated the negative effect of the withdrawal of overused analgesics and may be recommended for out-patient use.

  5. Evaluation of chitosan–anionic polymers based tablets for extended-release of highly water-soluble drugs

    Directory of Open Access Journals (Sweden)

    Yang Shao

    2015-02-01

    Full Text Available The objective of this study is to develop chitosan–anionic polymers based extended-release tablets and test the feasibility of using this system for the sustained release of highly water-soluble drugs with high drug loading. Here, the combination of sodium valproate (VPS and valproic acid (VPA were chosen as the model drugs. Anionic polymers studied include xanthan gum (XG, carrageenan (CG, sodium carboxymethyl cellulose (CMC-Na and sodium alginate (SA. The tablets were prepared by wet granulation method. In vitro drug release was carried out under simulated gastrointestinal condition. Drug release mechanism was studied. Compared with single polymers, chitosan–anionic polymers based system caused a further slowdown of drug release rate. Among them, CS–xanthan gum matrix system exhibited the best extended-release behavior and could extend drug release for up to 24 h. Differential scanning calorimetry (DSC and Fourier transform infrared spectroscopy (FTIR studies demonstrated that polyelectrolyte complexes (PECs were formed on the tablet surface, which played an important role on retarding erosion and swelling of the matrix in the later stage. In conclusion, this study demonstrated that it is possible to develop highly water-soluble drugs loaded extended-release tablets using chitosan–anionic polymers based system.

  6. Differential scanning calorimetry as a screening technique in compatibility studies of acyclovir extended release formulations

    Energy Technology Data Exchange (ETDEWEB)

    Barboza, Fernanda M.; Vecchia, Debora D. [Universidade Estadual de Ponta Grossa (UEPG), PR (Brazil). Dept. de Ciencias Farmaceuticas. Lab. de Controle de Qualidade; Tagliari, Monika P.; Ferreira, Andrea Granada; Silva, Marcos A.S.; Stulzer, Hellen K., E-mail: hellen.stulzer@gmail.co [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Dept. de Ciencias Farmaceuticas. Lab. de Controle de Qualidade

    2009-07-01

    Acyclovir (ACV) has been investigated during the past years, mainly due to its antiviral activity. Assessment of possible incompatibility between an active component and different excipients along with the evaluation of thermal stability are crucial parts of a normal study prior to the final formulation setting of a medicine. Thermal analysis studies were used as important and complementary tools during pre-formulation to determine the compatibility of drug excipients with the purpose of developing an acyclovir extended release formulation. Fourier transform infrared spectroscopy and X-ray powder diffraction analyses were also realized. The results showed that ACV only exhibited interaction which could influence the stability of the product in the binary mixtures of ACV/magnesium stearate. (author)

  7. Stimulant therapy in the management of ADHD: mixed amphetamine salts (extended release).

    Science.gov (United States)

    Faraone, Stephen V

    2007-09-01

    The efficacy of amphetamines in the management of attention-deficit/hyperactivity disorder (ADHD) is well established. However, their value in improving the symptoms of ADHD has been compromised by concerns about compliance, abuse potential and adverse events. An extended-release formulation of mixed amphetamine salts (MAS XR) provided the first long-acting amphetamine formulation, and thus, filled an important gap in available treatments for ADHD. MAS XR has been shown to improve ADHD symptoms in children, adolescents and adults in both short- and long-term studies. The drug is generally well tolerated in clinical trials. Although its safety profile in patients with concomitant cardiovascular conditions in a real-world setting has yet to be fully evaluated, a tolerability study of mixed amphetamine salts in adults with ADHD who were being treated for primary essential hypertension showed that these patients can be safely treated with MAS XR.

  8. Update on tolterodine extended-release for treatment of overactive bladder

    Directory of Open Access Journals (Sweden)

    Tola Omotosho

    2010-11-01

    Full Text Available Tola Omotosho, Chi Chiung Grace ChenWomen’s Center for Pelvic Health, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD, USAAbstract: Overactive bladder is a prevalent condition which negatively impacts quality of life and puts a significant economical burden on society. First-line therapy often includes pharmacotherapy with antimuscarinic medications, and numerous research studies have demonstrated that tolterodine extended-release (ER is an efficacious and tolerable formulation of this class of medication. This review provides an update on the clinical use of tolterodine ER, detailing the current literature on its efficacy, tolerability, adverse effects, and comparability with other commonly prescribed medications for the treatment of overactive bladder.Keywords: antimuscarinics, efficacy, quality of life, overactive bladder, tolterodine, urgency, urge urinary incontinence

  9. A stable fixed-dose combination tablet of pseudoephedrine and KOB extracts for the extended release.

    Science.gov (United States)

    Hwang, C-J; Park, M-H; Jung, H-W; Park, Y-K; Kim, Y-H; Kang, J-S; Cho, C-W

    2013-11-01

    Allergic rhinitis (AR) is characterized by inflammation of the nasal mucosa with hypersensitivity resulting from seasonal or perennial responses to specific environmental allergens and by symptoms like nasal rubbing, sneezing, rhinorrhea, lacrimation, nasal congestion and obstruction, and less frequently cough. KOB extracts, which is a polyherbal medicine consisting of 5 different herbs (Atractylodes macrocephala, Astragalus membranaceus, Saposhnikovia divaricata, Ostericum koreanum and Scutellaria baicalensis) had commonly been used for the treatment of various allergic diseases showed an anti-allergic effect by modulating mast cell-mediated allergic responses in allergic rhinitis, recently. On the other hand, pseudoephedrine is a sympathomimetic amine commonly used to relieve congestion in patients with allergic rhinitis and common colds. Considering the KOB's therapeutic mechanism, the combination with pseudoephedrine would be suitable for allergic rhinitis. This study is to obtain an effective extended release formulation using pseudoephedrine and KOB extracts to reduce side effects of drug due to repeated dosing and improve the compliance of patients for treatment of rhinitis and nasal decongestion. So, the fixed-dose combination tablet of pseudoephedrine and KOB extracts was prepared by direct compression and characterized by drug content, flowing characteristics and dissolution test. The drug content of baicalin of KOB extracts was within the range of 95-105% except for T1 formulation. The hardness and friability values of all formulations ranged from 9 to 13 kp and less than 1%, respectively. Taken together, T4 or T8 could be a stable fixed-dose combination tablet for extended release of pseudoephedrine and KOB extracts for nasal rhinitis.

  10. The management of schizophrenia: focus on extended-release quetiapine fumarate

    Directory of Open Access Journals (Sweden)

    Peuskens J

    2011-09-01

    Full Text Available Joseph Peuskens Universitair Psychiatrisch Centrum KU Leuven, Campus St Jozef Kortenberg, Kortenberg, Belgium Abstract: Effective management of schizophrenia remains a significant clinical challenge. While antipsychotic medications have proven efficacy in this disease, there remains an opportunity to further improve symptom control and long-term relapse prevention. Also, a number of factors, including tolerability and complex dosing regimens, can result in nonadherence to medication. Quetiapine is an atypical antipsychotic with proven efficacy and an established tolerability profile in schizophrenia. The once-daily extended-release formulation (quetiapine XR offers a simplified dosing regimen and titration schedule. Short-term clinical studies have shown that quetiapine XR (400–800 mg/d is efficacious in the acute treatment of schizophrenia, while a long-term study has shown that quetiapine XR was significantly more effective than placebo at preventing relapse. Furthermore, an investigation in which stable patients switched from the immediate-release formulation (quetiapine IR to quetiapine XR showed that quetiapine XR is generally well tolerated and has no loss of efficacy compared with quetiapine IR. In patients who experienced insufficient efficacy or poor tolerability on their previous antipsychotic, switching to quetiapine XR significantly improved efficacy compared with the previous treatment. In conclusion, quetiapine XR is an effective and generally well tolerated treatment for schizophrenia. Furthermore, once-daily dosing may improve patient adherence, which may impact positively on patient outcomes. Keywords: adherence, atypical antipsychotics, adverse events

  11. Oxybutynin extended release for the management of overactive bladder: a clinical review

    Directory of Open Access Journals (Sweden)

    AM Arisco

    2009-05-01

    Full Text Available AM Arisco, EK Brantly, SR KrausUniversity of Texas Health Science Center at San Antonio, Department of Urology, San Antonio, Texas, USAAbstract: Overactive bladder (OAB is a common condition which negatively impacts the quality of life of afflicted patients. This can result in alterations in social interactions at home, in the workplace and in the community, often leading to depression and poor self esteem as well as loss of productivity. Traditional mainstays of treatment include both behavioral therapy and pharmacotherapy. Oxybutynin immediate release (IR represents the first such medication approved by the FDA specifically for treatment of OAB in 1975. Nevertheless, bothersome side effects in addition to thrice daily dosing often led to treatment cessation which raised the question that patients may actually prefer to live with their OAB symptoms rather than incur side effects or complex dosing schemes. Pharmacological advances ultimately led to development of a long-acting formulation of oxybutynin in the form of oxybutynin extended release (ER with the hope that this drug would maintain efficacy while decreasing bothersome side effects and improve compliance with the convenience of once daily dosing regimen. This paper will review the major clinical studies involving oxybutynin ER as well as its role in different patient populations and potential concerns with its use.Keywords: overactive bladder, urinary urge incontinence, antimuscarinic, oxybutynin 

  12. Oxybutynin extended release for the management of overactive bladder: a clinical review.

    Science.gov (United States)

    Arisco, A M; Brantly, E K; Kraus, S R

    2009-09-21

    Overactive bladder (OAB) is a common condition which negatively impacts the quality of life of afflicted patients. This can result in alterations in social interactions at home, in the workplace and in the community, often leading to depression and poor self esteem as well as loss of productivity. Traditional mainstays of treatment include both behavioral therapy and pharmacotherapy. Oxybutynin immediate release (IR) represents the first such medication approved by the FDA specifically for treatment of OAB in 1975. Nevertheless, bothersome side effects in addition to thrice daily dosing often led to treatment cessation which raised the question that patients may actually prefer to live with their OAB symptoms rather than incur side effects or complex dosing schemes. Pharmacological advances ultimately led to development of a long-acting formulation of oxybutynin in the form of oxybutynin extended release (ER) with the hope that this drug would maintain efficacy while decreasing bothersome side effects and improve compliance with the convenience of once daily dosing regimen. This paper will review the major clinical studies involving oxybutynin ER as well as its role in different patient populations and potential concerns with its use.

  13. Exenatide Extended-Release: An Updated Review of Its Use in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Syed, Yahiya Y; McCormack, Paul L

    2015-07-01

    Exenatide extended-release (exenatide ER) [Bydureon(®)] is a glucagon-like peptide-1 receptor agonist, approved for the treatment of type 2 diabetes mellitus. It is injected subcutaneously by patients once weekly, with no dose titration required. This article updates an earlier review of exenatide ER in the management of type 2 diabetes, focusing on recently published data. In randomized, controlled trials, adjunctive exenatide ER 2 mg once weekly for 24-30 weeks significantly improved glycaemic control and reduced bodyweight in patients with inadequately controlled type 2 diabetes despite diet plus exercise and/or oral antihyperglycaemic drugs (OADs). These beneficial effects of exenatide ER were maintained after up to 6 years of treatment. In patients receiving one or more OADs, addition of exenatide ER provided better glycaemic control than an immediate-release formulation of exenatide (exenatide twice daily), sitagliptin, pioglitazone, insulin glargine or insulin detemir, and was slightly less effective than liraglutide. In patients treated with diet plus exercise alone, adjunctive exenatide ER was noninferior to metformin and superior to sitagliptin, but was not noninferior to pioglitazone. Exenatide ER was generally well tolerated, with a low inherent risk of hypoglycaemia. The most common adverse events were mild to moderate gastrointestinal events, injection-site reactions and headache. Thus, exenatide ER is a useful treatment option in the management of type 2 diabetes. It offers a convenient, once-weekly regimen and can be administered by patients via a pen injection system or syringes and needles.

  14. Comparison of single-dose and multiple-dose pharmacokinetics between two formulations of hydrocodone bitartrate/acetaminophen: immediate-release versus biphasic immediate- release/extended release

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2015-09-01

    Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young4 1Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 2Independent Pharmaceuticals Professional, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 3Research and Development, 4Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA Objective: This study aimed to compare the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release (IR/extended-release (ER hydrocodone bitartrate (HB/acetaminophen (APAP and IR HB/APAP. Setting: The study was conducted in a contract research center. Participants: The study included healthy adults. Interventions: In a three-way crossover study, Study 1, participants received the following treatments: (A1 a single dose of IR/ER HB/APAP 7.5/325 mg one tablet, followed by one tablet every 12 hours (q12h; (B1 a single dose of IR/ER HB/APAP 7.5/325 mg two tablets, followed by two tablets q12h; (C1 a single dose of IR HB/APAP 7.5/325 mg two tablets (one tablet at hours 0 and 6, followed by one tablet q6h. In a two-way crossover study, Study 2, participants received the following treatments: (A2 an initial dose of IR/ER HB/APAP 7.5/325 mg three tablets, followed by two tablets q12h; (B2 three doses of IR HB/APAP 7.5/325 mg one tablet q4h, followed by one tablet q6h. Main outcome measures: PK values were compared, and adverse events were assessed. Results: Single-dose and steady-state area under the concentration–time curves for hydrocodone and APAP were similar for IR/ER and IR HB/APAP; the steady-state peak plasma concentrations (Cmax at steady state were also similar, but single-dose Cmax for hydrocodone was lower for IR/ER HB/APAP. For most PK parameters, 90% confidence intervals for geometric least squares mean ratios were not meaningfully different (80%–125%. Steady state was achieved in 2-3 days for IR/ER HB/APAP and in 2 days for IR HB/APAP. Median

  15. Evaluation of extended-release applications for solid dispersion hot-melt fluid bed coatings utilizing hydrophobic coating agents.

    Science.gov (United States)

    Kennedy, J P; Niebergall, P J

    1998-02-01

    A new hot-melt fluid bed coating method was evaluated for potential extended-release applications. Chlorpheniramine maleate (CPM) USP was chosen as a model drug. The assays for drug release and content uniformity were dictated by the USP Official Monograph for a Chlorpheniramine Maleate Extended-Release Capsule. The fluid bed chamber was charged with CPM-loaded nonpareils and hydrophobic coating agents in the solid state. The method consists of four processing stages: (a) warming, (b) preheating, (c) melting-spreading, and (d) cooling-congealing. Various hydrophobic coating agent candidates were evaluated for extended-release potential by a preliminary screen at a coating agent level of 1.5% (w/w). A beeswax coating agent was identified as the most promising candidate of the preliminary screen. After the level of beeswax was increased to 2.0%, the dissolution profile met all of the specifications of the USP Drug Release Test 1 for a CPM Extended-Release Capsule. The potency and content uniformity remained unchanged by the process. Dual coatings demonstrated a cumulative extension of release superior to the capability of a single coat. The new method is a viable alternative to hot-melt spray-coating methodologies. Organic solvents, spraying equipment, steam jackets, and/or heating tape are eliminated from the process. A reduction of equipment costs, setup time, and cleanup time may be realized. The method has demonstrated extended-release capabilities. No excessive attrition of potency or content uniformity has been noted. Additive, multiple coatings that have a cumulative effect on release retardation are feasible.

  16. Application of chrome azurol S for the extractive spectrophotometric determination of fluoxetine and fluvoxamine.

    Science.gov (United States)

    Starczewska, B; Mielech, K

    2000-08-15

    Chrome azurol S has been tested as a spectrophotometric reagent for the determination of fluoxetine (FXT) and fluvoxamine (FXM). It reacts in aqueous media with FXT and FXM forming coloured, sparingly soluble in water compounds. These compounds can be quantitatively extracted with some organic solvents. This property has been exploited for the development of the extractive spectrophotometric methods for the determination of fluoxetine and fluvoxamine.

  17. Influence of fluvoxamine on plasma interleukin-6 or clinical improvement in patients with major depressive disorder

    Science.gov (United States)

    Yoshimura, Reiji; Katsuki, Asuka; Atake, Kiyokazu; Hori, Hikaru; Igata, Ryohei; Konishi, Yuki

    2017-01-01

    Objectives The etiology of depression remains unknown. There is, however, a growing body of evidence that cytokines are involved in the pathophysiology of depression. The aim of this study is to investigate the effects of fluvoxamine on plasma interleukin-6 (IL-6) levels and on clinical improvement of the depressive state. Subjects and methods Thirty patients who met the DSM-IV criteria for major depressive disorder (MDD) were enrolled in the study. Thirteen were male and 17 were female, and their ages ranged from 26 to 70 years (mean ± standard deviation 45.0±14.2). The patients were treated with fluvoxamine for 8 weeks. The dosages of fluvoxamine varied among the patients and, based on ethical considerations, were not fixed. Results The fluvoxamine doses were positively related to plasma fluvoxamine levels (r =0.8798, P<0.001). A significant correlation was observed between the patients’ plasma IL-6 levels and their 17-item Hamilton Rating Scale for Depression (HAMD17) scores (r =0.4555, P=0.0010). A positive correlation was found between the delta plasma IL-6 (week 0–week 8) and the delta HAMD17 (week 0–week 8) (r =0.5226, P=0.002). Conclusion Effect of fluvoxamine on IL-6 is partially associated with its clinical efficacy for MDD. PMID:28243095

  18. Effect of the proton pump inhibitor omeprazole on the pharmacokinetics of extended-release formulations of oxybutynin and tolterodine.

    Science.gov (United States)

    Dmochowski, Roger; Chen, Andrew; Sathyan, Gayatri; MacDiarmid, Scott; Gidwani, Shalini; Gupta, Suneel

    2005-08-01

    This study assessed the effect of the proton pump inhibitor omeprazole on the bioavailability of the extended-release formulations of oxybutynin and tolterodine. Forty-four healthy volunteers received each of 4 treatments in a 4-period crossover design. The treatments consisted of osmotically controlled extended-release oxybutynin chloride tablets at 10 mg/d or extended-release tolterodine tartrate capsules at 4 mg/d, with and without preceding treatment with 20 mg omeprazole daily for 4 days. Blood samples collected predose and at scheduled time points for 36 hours postdose were analyzed for oxybutynin and its active metabolite, N-desethyloxybutynin, or tolterodine and its active 5-hydroxymethyl metabolite, as appropriate. The AUCinfinity ratios for oxybutynin and its metabolite with and without prior omeprazole fell within the 80% to 125% range (accepted as the criterion for bioequivalence), as did those for tolterodine and its active moiety. The peak concentration ratios for oxybutynin and metabolite also conformed to this range; those for tolterodine did not. Increasing gastric pH with omeprazole does not substantially alter the pharmacokinetic properties of extended-release oxybutynin but may alter those of extended-release tolterodine.

  19. Exenatide extended-release: a once weekly treatment for patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Mann KV

    2014-06-01

    Full Text Available Katherine V Mann,1 Philip Raskin2 1PharmD Consulting, LLC, Royal Oak, MD, USA; 2Department of Internal Medicine, Division of Endocrinology, the University of Texas Southwestern Medical Center, Dallas, TX, USA Background: This article reviews the clinical efficacy, safety, and patient outcomes literature on the first once weekly treatment for type 2 diabetes mellitus (T2DM, exenatide extended-release (ER. Methods: Relevant literature on exenatide ER and T2DM was identified through PubMed database searches from inception until April 2014. Results: Exenatide ER is the first medication for the treatment of T2DM dosed on a weekly schedule. Exenatide ER is a glucagon-like peptide-1 (GLP-1 receptor agonist, the third to be approved in the US, and is associated with a low risk of hypoglycemia, may result in weight loss, and has proven to be a safe and effective treatment for T2DM. Exenatide ER reduces A1c levels by decreasing fasting and postprandial hyperglycemia. The most common adverse events are gastrointestinal in nature, which are lesser in frequency than those observed with short-acting exenatide. Exenatide ER has been shown to be more effective than exenatide twice daily and slightly less efficacious than liraglutide. Exenatide ER is useful as monotherapy and in combination with other oral antidiabetic drugs. Conclusion: Once weekly treatment options for diabetes such as exenatide ER have the potential to offer substantial convenience for patients who have high medication burden and poor medication adherence. Keywords: type 2 diabetes mellitus, long-acting release, GLP-1 receptor agonists

  20. Crawling The Web for Libre: Selecting, Integrating, Extending and Releasing Open Source Software

    Science.gov (United States)

    Truslove, I.; Duerr, R. E.; Wilcox, H.; Savoie, M.; Lopez, L.; Brandt, M.

    2012-12-01

    Libre is a project developed by the National Snow and Ice Data Center (NSIDC). Libre is devoted to liberating science data from its traditional constraints of publication, location, and findability. Libre embraces and builds on the notion of making knowledge freely available, and both Creative Commons licensed content and Open Source Software are crucial building blocks for, as well as required deliverable outcomes of the project. One important aspect of the Libre project is to discover cryospheric data published on the internet without prior knowledge of the location or even existence of that data. Inspired by well-known search engines and their underlying web crawling technologies, Libre has explored tools and technologies required to build a search engine tailored to allow users to easily discover geospatial data related to the polar regions. After careful consideration, the Libre team decided to base its web crawling work on the Apache Nutch project (http://nutch.apache.org). Nutch is "an open source web-search software project" written in Java, with good documentation, a significant user base, and an active development community. Nutch was installed and configured to search for the types of data of interest, and the team created plugins to customize the default Nutch behavior to better find and categorize these data feeds. This presentation recounts the Libre team's experiences selecting, using, and extending Nutch, and working with the Nutch user and developer community. We will outline the technical and organizational challenges faced in order to release the project's software as Open Source, and detail the steps actually taken. We distill these experiences into a set of heuristics and recommendations for using, contributing to, and releasing Open Source Software.

  1. Clinical utility of guanfacine extended release in the treatment of ADHD in children and adolescents

    Directory of Open Access Journals (Sweden)

    Bello NT

    2015-06-01

    Full Text Available Nicholas T Bello Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Abstract: Attention deficit hyperactivity disorder (ADHD is the most common psychiatric illness in children and adolescents. Several stimulant medications, such as methylphenidate and amphetamine derivatives, are available to treat ADHD in pediatric patients. Nonstimulant medications are more preferred by some parents, other caregivers, and patients because they lack the abuse potential of stimulant medications. In the US, one available nonstimulant option is guanfacine extended release (XR. As a selective α2A adrenergic receptor, guanfacine acts on the central noradrenergic pathways and cortical noradrenergic targets to improve working memory and attention. The XR formulation of guanfacine, compared with the immediate-release formulation, is more effective for the long-term management of ADHD and is associated with fewer adverse effects. Available data also indicate that guanfacine XR is superior to atomoxetine and is as effective as the nonselective α2 adrenergic receptor agonist, clonidine XR. The most common adverse effects associated with guanfacine XR are somnolence, fatigue, bradycardia, and hypotension. Somnolence is the most often cited reason for discontinuation. Guanfacine XR is also labeled for use as an adjuvant to stimulant treatment for ADHD. A similar profile of adverse effects as reported with monotherapy is reported when guanfacine XR is “added on” to stimulant therapy with somnolence as the most commonly reported adverse event. This review discusses the clinical efficacy and patient preference of guanfacine XR based on available published data on the safety, relative effectiveness, and tolerance of this medication to treat ADHD. Keywords: Intuniv, norepinephrine, prefrontal cortex, locus coeruleus, impulsivity, inattentive

  2. Extended release of hyaluronic acid from hydrogel contact lenses for dry eye syndrome.

    Science.gov (United States)

    Maulvi, Furqan A; Soni, Tejal G; Shah, Dinesh O

    2015-01-01

    Current dry eye treatment includes delivering comfort enhancing agents to the eye via eye drops, but low residence time of eye drops leads to low bioavailability. Frequent administration leads to incompliance in patients, so there is a great need for medical device such as contact lenses to treat dry eye. Studies in the past have demonstrated the efficacy of hyaluronic acid (HA) in the treatment of dry eyes using eye drops. In this paper, we present two methods to load HA in hydrogel contact lenses, soaking method and direct entrapment. The contact lenses were characterized by studying their optical and physical properties to determine their suitability as extended wear contact lenses. HA-laden hydrogel contact lenses prepared by soaking method showed release up to 48 h with acceptable physical and optical properties. Hydrogel contact lenses prepared by direct entrapment method showed significant sustained release in comparison to soaking method. HA entrapped in hydrogels resulted in reduction in % transmittance, sodium ion permeability and surface contact angle, while increase in % swelling. The impact on each of these properties was proportional to HA loading. The batch with 200-μg HA loading showed all acceptable values (parameters) for contact lens use. Results of cytotoxicity study indicated the safety of hydrogel contact lenses. In vivo pharmacokinetics studies in rabbit tear fluid showed dramatic increase in HA mean residence time and area under the curve with lenses in comparison to eye drop treatment. The study demonstrates the promising potential of delivering HA through contact lenses for the treatment of dry eye syndrome.

  3. Randomized, double-blind, multicenter evaluation of pramipexole extended release once daily in early Parkinson's disease.

    Science.gov (United States)

    Hauser, Robert A; Schapira, Anthony H V; Rascol, Olivier; Barone, Paolo; Mizuno, Yoshikuni; Salin, Laurence; Haaksma, Monika; Juhel, Nolwenn; Poewe, Werner

    2010-11-15

    The objective of this study was to evaluate the efficacy and safety of pramipexole extended release (ER) administered once daily in early Parkinson's disease (PD). Pramipexole immediate release (IR) administered three times daily (TID) is an efficacious and generally well-tolerated treatment for PD. A pramipexole ER formulation is now available. We performed a randomized, double-blind, placebo and active comparator-controlled trial in subjects with early PD. The primary efficacy and safety evaluation of pramipexole ER compared with placebo took place at week 18. Two hundred fifty-nine subjects were randomized 2:2:1 to treatment with pramipexole ER once daily, pramipexole IR TID, or placebo. Levodopa rescue was required by 7 subjects in the placebo group (14%), 3 subjects in the pramipexole ER group (2.9%, P = 0.0160), and 1 subject in the pramipexole IR group (1.0%, P = 0.0017). Adjusted mean [standard error (SE)] change in Unified Parkinson Disease Rating Scale (UPDRS) II [activities of daily living (ADL)] + III (motor) scores from baseline to week 18, including post-levodopa rescue evaluations, was -5.1 (1.3) in the placebo group, -8.1 (1.1) in the pramipexole ER group (P = 0.0282), and -8.4 (1.1) in the pramipexole IR group (P = 0.0153). Adjusted mean (SE) change in UPDRS ADL + motor scores, censoring post-levodopa rescue data, was -2.7 (1.3) in the placebo group, -7.4 (1.1) in the pramipexole ER group (P = 0.0010), and -7.5 (1.1) in the pramipexole IR group (P = 0.0006). Adverse events more common with pramipexole ER than placebo included somnolence, nausea, constipation, and fatigue. Pramipexole ER administered once daily was demonstrated to be efficacious compared with placebo and provided similar efficacy and tolerability as pramipexole IR administered TID.

  4. Pramipexole extended-release: a review of its use in patients with Parkinson's disease.

    Science.gov (United States)

    Frampton, James E

    2014-12-01

    Pramipexole, a non-ergolinic, D3-preferring dopamine agonist (DA), is well established as a treatment option for motor symptoms at all stages of Parkinson's disease (PD). It is administered orally and is available as both a three-times daily immediate-release (IR) formulation and a once-daily extended-release (ER) formulation (Mirapex(®) ER, Mirapexin(®) ER; Pexola(®) ER, Sifrol(®) ER). The two formulations are bioequivalent; the majority (>80 %) of patients can be switched overnight from pramipexole IR to ER without the need for dosage adjustment. In terms of improving activities of daily living and motor function in short-term (≤33-week), double-blind studies, pramipexole ER was noninferior to pramipexole IR and significantly more effective than placebo as monotherapy in patients with early PD, and similar to pramipexole IR and significantly more effective than placebo as adjunctive therapy to levodopa in patients with advanced PD. In long-term (80-week) extensions of these trials, open-label treatment with pramipexole ER was associated with sustained symptomatic benefit. Moreover, the majority of extension participants who responded to a simple convenience questionnaire expressed a preference for once-daily over three-times daily dosing. Pramipexole ER was generally well tolerated in clinical trials; no new or unexpected safety signals were identified compared with the IR formulation. Head-to-head trials are needed in order to fully define the role of pramipexole ER relative to other once-daily formulations of DAs (oral ropinirole and transdermal rotigotine). Nonetheless, by reducing the pill burden, the ER formulation of pramipexole provides a more convenient alternative to the IR formulation; studies specifically testing whether this translates into improved patient compliance and symptom control are worthwhile.

  5. Patient considerations in early management of Parkinson’s disease: focus on extended-release pramipexole

    Directory of Open Access Journals (Sweden)

    Salawu FK

    2012-01-01

    Full Text Available Fatai Kunle SalawuDivision of Neurology, Department of Medicine, Federal Medical Centre Yola, Adamawa State, NigeriaAbstract: This article reviews the role of an extended-release formulation of pramipexole in the treatment of Parkinson’s disease at an early stage. Pramipexole is a nonergot D2/D3 synthetic aminobenzothiazole derivative that is effective as monotherapy in early disease and as an adjunct to levodopa in patients with motor fluctuations. Although levodopa is the current “gold standard” for treatment of Parkinson’s disease, its effectiveness fades rapidly and its use results in serious motor fluctuations (on-off, wearing-off, freezing, involuntary movements for most patients with the disease. Pramipexole has selective actions at dopamine receptors belonging to the D2 subfamily, where it possesses full activity similar to dopamine itself. Its preferential affinity for the D3 receptor subtype could contribute to its efficacy in the treatment of both the motor and psychiatric symptoms of Parkinson’s disease. The best approach to medical management of early Parkinson’s disease remains controversial. While enormous progress has been made in the treatment of the disease, challenges still remain. A variety of treatment-related and patient-related factors must be taken into account when making these decisions. The current approach to treatment of early Parkinson’s disease depends in part on individual patient factors, including age, severity and nature of symptoms and their impact, presence of cognitive dysfunction, possible underlying behavioral factors predisposing to impulse control disorders, and other comorbidities. Today, the once-daily extended-release formulation of pramipexole offers the advantages of easy continuous delivery of drug and convenience to patients, particularly early in the disease when monotherapy is the rule. Thus, a new “levodopa-sparing” paradigm for treating Parkinson’s disease may now be

  6. Paliperidone extended-release: does it have a place in antipsychotic therapy?

    Directory of Open Access Journals (Sweden)

    Carlos Schönfeldt-Lecuona

    2011-03-01

    Full Text Available Maximilian Gahr1,*, Markus A Kölle1,*, Carlos Schönfeldt-Lecuona1, Peter Lepping2, Roland W Freudenmann11Department of Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany; 2Department of Psychiatry, Glyndwr University, Wales, UK *Both authors contributed equally and their order was determined by coin toss.Abstract: Paliperidone (9-hydroxy-risperidone, the active metabolite of risperidone, was approved for treating schizophrenia worldwide in 2006 as paliperidone extended-release (PER, and became the first second-generation antipsychotic specifically licensed for treating schizoaffective disorder in 2009. However, at the same time, its comparatively high cost gave rise to concerns about the cost-effectiveness of PER as compared with its precursor, risperidone. This paper reviews the existing knowledge of the pharmacology, kinetics, efficacy, tolerability, and fields of application of PER, and compares PER with risperidone in order to determine whether it has a place in antipsychotic therapy. An independent assessment of all relevant publications on PER published until July 2010 was undertaken. PER has a unique pharmacological profile, including single dosing, predominantly renal excretion, low drug–drug interaction risk, and differs from risperidone in terms of mode of action and pharmacokinetics. High-level evidence suggests that PER is efficacious and safe in schizophrenia, schizoaffective disorder, and acute manic episodes. There is a striking lack of published head-to-head comparisons between PER and risperidone, irrespective of indication. Low-level evidence shows a lower risk for hyperprolactinemia and higher patient satisfaction with PER than with risperidone. PER adds to the still limited arsenal of second-generation antipsychotics. In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of PER which would justify its substantially

  7. Exenatide extended-release: a review of its use in type 2 diabetes mellitus.

    Science.gov (United States)

    Scott, Lesley J

    2012-08-20

    Subcutaneous exenatide extended-release (ER; Bydureon™; also known as exenatide once weekly), a glucagon-like peptide-1 receptor agonist, provides a convenient, simple, once-weekly regimen that is approved in adult patients with type 2 diabetes as adjunctive monotherapy to diet plus exercise (in the US; not as first-line therapy) and/or as combination therapy with specific oral antihyperglycaemic drugs (OADs) in patients with inadequately controlled type 2 diabetes despite treatment with these OADs (US and Europe). This article reviews the clinical efficacy and tolerability of exenatide ER in the treatment of adult patients with type 2 diabetes and gives a brief overview of its pharmacological properties. In several short-term (24-30 weeks) well designed trials, adjunctive subcutaneously injectable exenatide ER once weekly, as monotherapy or in combination with OADs, significantly improved glycaemic control, bodyweight and some surrogate markers of cardiovascular risk in adult patients with inadequately controlled type 2 diabetes despite diet and exercise and/or treatment with OADs. Furthermore, the beneficial effects of adjunctive exenatide ER therapy were sustained in extension studies of up to 3 years of treatment. Overall, the intensity of glycaemic control with exenatide ER was generally better than that observed with the exenatide immediate-release formulation (twice daily), sitagliptin or insulin glargine. Exenatide ER was shown to be noninferior to metformin in terms of glycaemic efficacy, but did not meet the criteria for noninferiority versus liraglutide. In treatment-naive patients, exenatide ER treatment did not meet noninferiority criteria versus pioglitazone, whereas in treatment-experienced patients, exenatide ER provided better glycaemic control than pioglitazone. Improvements in glycaemic control with exenatide ER and, in general, with other antihyperglycaemic agents were reflected in significant improvements from baseline in treatment

  8. A crossover comparison of extended release felodipine with prolonged action nifedipine in hypertension.

    Science.gov (United States)

    Moncica, I; Oh, P I; ul Qamar, I; Scolnik, D; Arbus, G S; Hebert, D; Balfe, J W; Koren, G

    1995-01-01

    In a crossover design, control of blood pressure by extended release felodipine was compared with control by prolonged action nifedipine in 21 children with renal hypertension. Compliance with once daily felodipine was higher than with nifedipine, at 95.6 (SEM 2.7)% v 78.9 (6.0)% (p = 0.02). Mean diastolic blood pressure was lower during the day with felodipine than with nifedipine, at 77.6 (2.4) v 84.4 (2.8) mm Hg (p = 0.05). Similarly, blood pressure load (the percentage of the day during which the child had blood pressure exceeding the upper limits of normal for age) was lower for felodipine than for nifedipine: 43.5 (5.5)% v 61.3 (6.3)%. There was an opposite trend during the night, though this did not reach statistical significance. These data suggest that once a day felodipine is effective in children with hypertension. This may be because of improved compliance. PMID:7574861

  9. Opioid rotation with extended-release opioids: where should we begin?

    Directory of Open Access Journals (Sweden)

    Nalamachu S

    2011-12-01

    Full Text Available Srinivas NalamachuInternational Clinical Research Institute and Pain Management Institute, Overland Park, KS, USAAbstract: Opioid rotation is a common and necessary clinical practice in the management of chronic non-cancer pain to improve therapeutic efficacy with the lowest opioid dose. When dose escalations fail to achieve adequate analgesia or are associated with intolerable side effects, a trial of a new opioid should be considered. Much of the scientific rationale of opioid rotation is based on the wide interindividual variability in sensitivity to opioid analgesics and the novel patient response observed when introducing an opioid-tolerant patient to a new opioid. This article discusses patient indicators for opioid rotation, the conversion process between opioid medications, and additional practical considerations for increasing the effectiveness of opioid therapy during a trial of a new opioid. A Patient vignette that demonstrates a step-wise approach to opioid rotation is also presented.Keywords: extended-release opioids, chronic pain, opioid rotation

  10. Extended-Release Naltrexone: A Qualitative Analysis of Barriers to Routine Use.

    Science.gov (United States)

    Alanis-Hirsch, Kelly; Croff, Raina; Ford, James H; Johnson, Kim; Chalk, Mady; Schmidt, Laura; McCarty, Dennis

    2016-03-01

    The Medication Research Partnership (a national health plan and nine addiction treatment centers contracted with the health plan) sought to facilitate the adoption of pharmacotherapy for alcohol and opioid use disorders. Qualitative analysis of interviews with treatment center change leaders, individuals working for the manufacturer and its technical assistance contractor, and health plan managers extracted details on the processes used to order, store, bill for, and administer extended-release naltrexone. Qualitative themes were categorized using domains from the Consolidated Framework for Implementation Research (intervention characteristics, outer setting, inner setting, and provider characteristics). Characteristics of XR-NTX that inhibited use included the complexity of ordering and using the medication; cost was also a barrier. Outer setting barriers reflected patient needs and external health plan policies on formulary coverage, benefit management, and reimbursement. Program structures, the lack of physician linkages, a culture resistant to the use of medication, and unease with change were inner setting elements that limited use of XR-NTX. Patient stereotypes and a lack of knowledge about XR-NTX affected practitioner willingness to treat patients and prescribe XR-NTX. The Consolidated Framework for Implementation Research provided a useful lens to understand and interpret the processes affecting access to XR-NTX.

  11. Effects of extended-release niacin with laropiprant in high-risk patients

    DEFF Research Database (Denmark)

    Landray, Martin J; Haynes, Richard; Hopewell, Jemma C

    2014-01-01

    BACKGROUND: Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein (HDL) choleste......BACKGROUND: Patients with evidence of vascular disease are at increased risk for subsequent vascular events despite effective use of statins to lower the low-density lipoprotein (LDL) cholesterol level. Niacin lowers the LDL cholesterol level and raises the high-density lipoprotein (HDL...... revascularization). RESULTS: During a median follow-up period of 3.9 years, participants who were assigned to extended-release niacin-laropiprant had an LDL cholesterol level that was an average of 10 mg per deciliter (0.25 mmol per liter as measured in the central laboratory) lower and an HDL cholesterol level......, respectively; rate ratio, 0.96; 95% confidence interval [CI], 0.90 to 1.03; P=0.29). Niacin-laropiprant was associated with an increased incidence of disturbances in diabetes control that were considered to be serious (absolute excess as compared with placebo, 3.7 percentage points; P

  12. Potential role of gabapentin and extended- release gabapentin in the management of menopausal hot flashes

    Directory of Open Access Journals (Sweden)

    Yadav M

    2013-08-01

    Full Text Available Manisha Yadav, Judith Volkar Center for Specialized Women’s Health, Cleveland Clinic Foundation, Cleveland, Ohio, USA Abstract: About 80% of postmenopausal women experience vasomotor symptoms, such as hot flashes and night sweats – symptoms that are associated with sleep disruption and can lead to fatigue and mood changes. Moreover, hot flashes can be embarrassing for women, causing difficulties at work and in their social lives. Many therapies have been advocated for relief of vasomotor symptoms, but only hormone therapy has been US Food and Drug Administration approved. However, after the Women's Health Initiative Study suggested that there was a correlation between hormone therapy and increased risk for breast cancer and cardiovascular events, many women stopped taking hormone therapy, and many do not want to initiate it. Hormone therapy is also contraindicated in certain women, such as those with a history of hormone-stimulated cancer like breast and uterine cancer. Gabapentin (Neurontin has shown efficacy in relieving vasomotor symptoms and is used as off-label for this indication. A new extended-release formulation of gabapentin has also shown efficacy in treating hot flashes and improving sleep quality with possibly fewer side effects than regular gabapentin. Keywords: Hot flushes, vasomotor symptoms, postmenopausal, hormone-sensitive cancer, non-hormonal therapy, gastric-retentive, Breeze

  13. Tapentadol extended release in the management of peripheral diabetic neuropathic pain

    Directory of Open Access Journals (Sweden)

    Vadivelu N

    2015-01-01

    Full Text Available Nalini Vadivelu,1 Alice Kai,2 Benjamin Maslin,1 Gopal Kodumudi,3 Aron Legler,1 Jack M Berger4 1Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA; 2Stony Brook University School of Medicine, Stony Brook, NY, USA; 3Department of Structural and Cellular Biology, Tulane University, New Orleans, LA, USA; 4Department of Anesthesiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Abstract: Tapentadol, a µ-opioid agonist and norepinephrine reuptake inhibitor, has been found to be an effective medication for a wide variety of chronic pain conditions, including back pain, cancer-related pain, and arthritic pain. It has also been found to have fewer gastrointestinal side effects than more traditional opioid-based therapies. More recently, tapentadol extended release has been demonstrated to be effective in the management of painful diabetic neuropathy, an often debilitating condition affecting approximately one-third of all patients with diabetes. This review highlights the most up-to-date basic and clinical studies by focusing on the mechanisms of action of tapentadol and its clinical efficacy, especially with regard to painful diabetic neuropathy. Keywords: chronic pain, neuropathic pain, pharmacology, analgesia, pain management

  14. Gabapentin Extended-Release - Depomed: Gabapentin ER, Gabapentin Gastric Retention, Gabapentin GR.

    Science.gov (United States)

    2007-01-01

    Depomed is developing an extended-release (ER) oral formulation of gabapentin, a GABA receptor agonist commonly used for the treatment of epilepsy and seizures, neuropathic pain and hot flushes. Gabapentin ER is based on the company's proprietary AcuForm drug delivery technology, which is part of the Gastric Retention (GR) family of technologies; this offers improved drug absorption and bioavailability compared with the existing immediate-release formulation of gabapentin (Neurontin), making gabapentin ER suitable for twice-daily dosing. The product is in clinical development for the treatment of postherpetic neuralgia and diabetic neuropathies in the US. Additionally, Depomed has commenced a phase II trial of gabapentin ER in postmenopausal patients with hot flushes. Depomed's AcuForm platform is based on polymer technology that provides targeted drug delivery for a variety of compounds. Following ingestion, AcuForm tablets swell and are retained for 6-8 hours in the stomach, enabling controlled and prolonged release of gabapentin to the upper intestinal tract; this extends the time of drug delivery to the small intestine for complete and safe elimination via the lower intestinal track. Gabapentin ER is available for licensing. Depomed acquired exclusive development and commercialisation rights to gabapentin ER in September 2003 via its subsidiary, Depomed Development Ltd (DDL). Depomed is not required to pay upfront license fees, but will make royalty and milestone payments to DDL upon successful commercialisation of gabapentin ER. Gabapentin ER was originally developed by DDL, a joint venture between Depomed and Elan established in January 2000 to design products using the GR family of technologies. However, in efforts to restructure joint venture relationships, Elan withdrew from operational involvement of DDL in September 2003, and Depomed has gained full ownership of DDL. Depomed sublicensed exclusive rights to a US patent (held by the University of Rochester

  15. Extended release microparticle-in-gel formulation of octreotide: Effect of polymer type on acylation of peptide during in vitro release.

    Science.gov (United States)

    Vaishya, Ravi D; Mandal, Abhirup; Patel, Sulabh; Mitra, Ashim K

    2015-12-30

    Polymeric microparticles (MPs)-in-gel formulations for extended delivery of octreotide were developed. We investigated influence of polymer composition on acylation of octreotide and kinetics of release during in vitro release from biodegradable polymeric formulations. Polycaprolactone (PCL), polylactic acid (PLA), polyglycolic acid (PGA) and polyethylene glycol (PEG) based triblock (TB≈PCL10k-PEG2k-PCL10k) and pentablock (PBA≈PLA3k-PCL7k-PEG2k-PCL7k-PLA3k and PBB≈PGA3k-PCL7k-PEG2k-PCL7k-PGA3k) polymers were investigated. Octreotide was encapsulated in MPs using methanol-oil/water emulsion solvent evaporation method. The particles were characterized for size, morphology, encapsulation efficiency, drug loading and in vitro release. Release samples were subjected to HPLC analysis for quantitation and HPLC-MS analysis for identification of native and chemically modified octreotide adducts. Entrapment efficiency of methanol-oil/water method with TB, PBA and PBB polymers were 45%, 60%, and 82%, respectively. A significant fraction of released octreotide was acylated from lactide and glycolide based PBA (53%) and PBB (92%) polymers. Substantial amount of peptide was not released from PBB polymers after 330 days of incubation. Complete release of octreotide was achieved from TB polymer over a period of 3 months with minimal acylation of peptide (13%). PCL based polymers resulted in minimal acylation of peptide and hence may be suitable for extended peptide and protein delivery. Conversely, polymers having PLA and PGA blocks may not be appropriate for peptide delivery due to acylation and incomplete release.

  16. Dalfampridine extended release tablets: 1 year of postmarketing safety experience in the US

    Directory of Open Access Journals (Sweden)

    Jara M

    2013-03-01

    Full Text Available Michele Jara,1 Graham Barker,2 Herbert R Henney 3rd1 1Acorda Therapeutics, Inc, Ardsley, NY, USA; 2Biogen Idec, Inc, Maidenhead, Berkshire, UK Background: Dalfampridine extended release tablets (dalfampridine-ER; prolonged-, modified, or sustained-release fampridine in some countries were approved in the US to improve walking in patients with multiple sclerosis, as demonstrated by improvement in walking speed. Postmarketing safety experience is available from exposure of approximately 46,000 patients in the US from product approval through March 2011. Objective: To provide a descriptive analysis of all spontaneously reported postmarketing adverse events (AEs for dalfampridine-ER since product launch. Methods: AE data were extracted from the safety database from product launch through March 31, 2011; AEs were classified using the Medical Dictionary for Regulatory Activities. Seizure cases were reviewed for patient demographics, time to event from treatment onset, and presence of additional risk factors. Results: The most frequently reported postmarketing AEs were similar to those reported during clinical development: dizziness, insomnia, balance disorder, headache, nausea, urinary tract infection, asthenia, and back pain (all included in US product labeling. New clinically significant findings are related to lack of efficacy and inappropriate dosing. Of the approximately 46,000 patients exposed, 85 seizures were reported (~5.4/1000 patient-years, of which 82 were reported or confirmed by a health care practitioner (~5.2/1000 patient-years. Beyond the intrinsic multiple sclerosis-related seizure risk, more than half of the 85 cases (62% had an additional potential risk factor for seizure including a previous history of convulsions, renal impairment, incorrect dosing, or use of concurrent medications with a labeled seizure risk. Duration of treatment prior to the seizure ranged from one dose to 365 days; 26/85 (31% patients suffered a seizure

  17. Effects of Extended-Release Guanfacine on ADHD Symptoms and Sedation-Related Adverse Events in Children with ADHD

    Science.gov (United States)

    Faraone, Stephen V.; Glatt, Stephen J.

    2010-01-01

    Objective: Guanfacine extended release (GXR) is a selective alpha[subscript 2A]-adrenoceptor agonist that is shown to be an effective nonstimulant treatment for the symptoms of attention-deficit/hyperactivity disorder. This report documents the time course and predictors of symptom efficacy and sedation-related adverse events (AEs) that emerge…

  18. Guanfacine Extended Release in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Placebo-Controlled Trial

    Science.gov (United States)

    Sallee, Floyd R.; McGough, James; Wigal, Tim; Donahue, Jessica; Lyne, Andrew; Biederman, Joseph

    2009-01-01

    A double-blind, 9-week, randomized trial was done to compare the efficacy of guanfacine extended release (GXR) with a placebo in treating children and adolescents with attention-deficit/hyperactivity disorders (ADHD). Results find a significant reduction in ADHD from baseline to endpoint for all daily doses of GXR which were measured at 1-, 2-,…

  19. 76 FR 68766 - Draft Blueprint for Prescriber Education for Long-Acting/Extended-Release Opioid Class-Wide Risk...

    Science.gov (United States)

    2011-11-07

    ... Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061...-acting and extended-release brand name and generic products and are formulated with the active... Dockets Management (see ADDRESSES) either electronic or written comments on the draft Blueprint. It...

  20. Baclofen novel gastroretentive extended release gellan gum superporous hydrogel hybrid system: in vitro and in vivo evaluation.

    Science.gov (United States)

    El-Said, Ibrahim A; Aboelwafa, Ahmed A; Khalil, Rawia M; ElGazayerly, Omaima N

    2016-01-01

    Baclofen is a centrally acting skeletal muscle relaxant with a short elimination half-life, which results in frequent daily dosing and subsequent poor patient compliance. The narrow absorption window of baclofen in the upper gastrointestinal tract limits its formulation as extended release dosage forms. In this study, baclofen extended release superporous hydrogel (SPH) systems, including conventional SPH, SPH composite and SPH hybrid (SPHH), were prepared aiming to increase the residence of baclofen at its absorption window. The applicability of different polymers, namely, gellan gum, guar gum, polyvinyl alcohol and gelatin, was investigated in preparation of SPHH systems. The prepared SPH systems were evaluated regarding weight and volume swelling ratio, porosity, mechanical properties, incorporation efficiency, degree of erosion and drug release. In vivo assessment was performed in dogs to evaluate gastric residence time by X-ray studies. In addition, the oral bioavailability of baclofen relative to commercially available Lioresal® immediate release tablets was also investigated. The novel baclofen gellan SPHH cross linked with calcium chloride was characterized by optimum mechanical properties, acceptable swelling properties as well as extended drug release. It also exhibited a prolonged plasma profile when compared to twice daily administered Lioresal®.

  1. An assessment of the clinical equivalence of valproate chrono and extended release divalproex formulations

    Directory of Open Access Journals (Sweden)

    Rajesh B

    2007-01-01

    Full Text Available Objective: No guideline currently exists to choose the clinically equivalent dose of divalproex extended release (ER formulation while switching over from valproate chrono formulation. To address this issue, we evaluated the serum valproate concentration following switch over from valproate chrono to divalproex ER in persons with epilepsy. Materials and Methods: An open label study was conducted in two parts, each for a period of two months. During Part I, patients on regular twice-daily dose of valproate chrono were switched over to once daily divalproex ER (DESVAL ER ® based on the dose escalation recommended when switching over from divalproex DR to ER formulation as the guideline. During Part II, we switched from valproate chrono to divalproex ER with same dosage. Serum valproate concentration, seizure frequency and side effects were assessed serially for two months after changeover and compared with the preswitch data. Results: During Part I, compared to the baseline level, there was a significant increase in mean serum valproate level at two months (67.0 ± 28.4 mg/ml versus 91.9 ± 3.5 mg/ml, P 0.004. With the same dose conversion during Part II, the mean valproate level did not significantly differ before and after the switch (81.5 mg/dl versus 85.7 mg/dl, P 0.08. The mean monthly seizure frequencies and serum ammonia levels did not change during either part. No significant adverse effects occurred. Conclusion: The results of this open label study with small number of patients need to be replicated among larger patient sample through a randomized control design before recommending same dose conversion from valproate chrono to divalproex ER without change in efficacy and tolerability,

  2. Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson's Disease.

    Science.gov (United States)

    Yun, Ji Young; Kim, Young Eun; Yang, Hui-Jun; Kim, Han-Joon; Jeon, Beomseok

    2017-01-01

    This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson's disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson's disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov.

  3. Distribution of dipyridamole in blood components among post-stroke patients treated with extended release formulation.

    Science.gov (United States)

    Serebruany, Victor; Sabaeva, Elena; Booze, Christopher; Atar, Oliver D; Eisert, Christian; Hanley, Dan

    2009-09-01

    Extended release dipyridamole (ERD) is widely used in patients after ischaemic stroke; however, the ability of this antithrombotic agent to be stored in different blood cells has never been explored in post-stroke patients. We hypothesised that since ERD is known to be highly lipophilic, the drug may be present not only in plasma, but also accumulated in platelets, leukocytes, and erythrocytes. Fifteen patients after documented ischaemic stroke were treated with Aggrenox (ERD and low-dose aspirin combination) BID for 30 days, and 12 of them completed the study. ERD concentrations in blood cells and platelet-poor plasma were measured by spectrofluorimetry at Baseline, Day 14, and Day 30 after the initiation of therapy. The background level of spectrofluorometry readings differs slightly among the blood components (132-211 ng/ml) due to the differences in the preparation of samples and cell isolation techniques. As expected, two weeks of ERD therapy produced steady-state plasma concentration of dipyridamole already at Day 14 (1,680 +/- 542 ng/ ml), followed by a slight not significant decrease at one month (1,619 +/- 408 ng/ml). Two weeks of therapy was sufficient to achieve a consistent dipyridamole accumulation in erythrocytes (361 +/- 43 ng/ml), but not in platelets (244 +/- 78 ng/ml), or leukocytes (275 +/- 49 ng/ml). In fact, white blood cells continued dipyridamole intake beyond 14 days period, and this increase (398 +/- 66 ng/ml) was significant (p = 0.02) at 30 days. Treatment with ERD in post-stroke patients resulted not only in achievement of therapeutic plasma dipyridamole concentrations, but also deposition of the drug in erythrocytes and leukocytes, but not in platelets. If confirmed, these data will affect our better understanding of dipyridamole pleiotropy, and may explain long-term benefit of ERD formulation.

  4. Neural correlates of adherence to extended-release naltrexone pharmacotherapy in heroin dependence

    Science.gov (United States)

    Wang, A-L; Elman, I; Lowen, S B; Blady, S J; Lynch, K G; Hyatt, J M; O'Brien, C P; Langleben, D D

    2015-01-01

    Injectable extended-release naltrexone (XRNTX) presents an effective therapeutic strategy for opioid addiction, however its utility could be hampered by poor adherence. To gain a better insight into this phenomenon, we utilized blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) in conjunction with a validated cue-induced craving procedure to examine neural correlates of XRNTX adherence. We operationalized treatment adherence as the number of monthly XRNTX injections (range: 0–3) administered to a group of fully detoxified heroin-dependent subjects (n=32). Additional outcomes included urine toxicology screening and self-reported tobacco use. The presented heroin-related visual cues reliably elicited heroin craving in all tested subjects. Nine, five, three and 15 of the participants, respectively, received zero, one, two and three XRNTX injections, predicted by the individual baseline fMRI signal change in response to the cues in the medial prefrontal cortex, a brain region involved in inhibitory self-control and emotional appraisal. The incidence of opioid-positive urines during the XRNTX therapy was low and remained about half the pre-treatment rate after the XRNTX ended. During the treatment, cigarette smoking behaviors followed patterns of opioid use, while cocaine consumption was increased with reductions in opioid use. The present data support the hypothesis that medial prefrontal cortex functions are involved in adherence to opioid antagonist therapy. A potential role of concurrent non-opioid addictive substances consumption during the XRNTX pharmacotherapy warrants further investigation. Our findings set the stage for further bio-behavioral investigations of the mechanisms of relapse prevention in opioid dependence. PMID:25781230

  5. Extended-release naltrexone modulates brain response to drug cues in abstinent heroin-dependent patients.

    Science.gov (United States)

    Langleben, Daniel D; Ruparel, Kosha; Elman, Igor; Loughead, James W; Busch, Elliot L; Cornish, James; Lynch, Kevin G; Nuwayser, Elie S; Childress, Anna R; O'Brien, Charles P

    2014-03-01

    Drug cues play an important role in relapse to drug use. Naltrexone is an opioid antagonist that is used to prevent relapse in opioid dependence. Central opioidergic pathways may be implicated in the heightened drug cue-reactivity, but the effects of the opioid receptors' blockade on the brain responses to drug cues in opioid dependence are unknown. To pursue this question, we studied 17 abstinent i.v. heroin users with brain functional magnetic resonance imaging (fMRI) during exposure to visual heroin-related cues and matched neutral images before and 10-14 days after an injection of extended-release naltrexone (XRNTX). Whole brain analysis of variance of fMRI data showed main effect of XRNTX in the medial frontal gyrus, precentral gyrus, cuneus, precuneus, caudate and the amygdala. fMRI response was decreased in the amygdala, cuneus, caudate and the precentral gyrus and increased in the medial frontal gyrus and the precuneus. Higher plasma levels of naltrexone's major metabolite, 6-beta-naltrexol, were associated with larger reduction in the fMRI response to drug cues after XRNTX in the precentral, caudate and amygdala clusters. The present data suggest that XRNTX pharmacotherapy of opioid-dependent patients may, respectively, decrease and potentiate prefrontal and limbic cortical responses to drug cues and that this effect might be related to the XRNTX metabolism. Our findings call for further evaluation of the brain fMRI response to drug-related cues and of the 6-beta-naltrexol levels as potential biomarkers of XRNTX therapeutic effects in patients with opioid dependence.

  6. Single-Dose Pharmacokinetic Study of Tramadol Extended-Release Tablets in Children and Adolescents.

    Science.gov (United States)

    Vandenbossche, Joris; Van Peer, Achiel; Richards, Henry

    2016-09-01

    Combined analyses from 2 open-label, phase-1 studies-the pharmacokinetic profile of tramadol and its metabolite (M1) following a single oral dose of tramadol extended release (ER) (25 to 100 mg) in children (7 to 11 years old; study 1: n = 37) and adolescents (12 to 17 years old; study 2: n = 38) with painful conditions-were historically compared with that of healthy adults following similar dosing. The dose-normalized area under the curve (DN AUC0-24h ) and maximum concentration (DN Cmax ) of tramadol and of M1 in children and in adolescents were lower than those in adults (children vs adults: tramadol, DN AUC0-24h 82.19%; DN Cmax 80.38%, P = .0031; M1, DN AUC0-24h 51.19%, DN Cmax 52.68%, P < .0001; adolescents vs adults: tramadol, DN AUC0-24h 89.56%, DN Cmax 84.01%; M1, DN AUC0-24h 85.28%, DN Cmax 83.03%, P = .0004). The arithmetic mean terminal elimination t1/2 of tramadol in children and adolescents was comparable to that in adults (children 8.4 hours; adolescents 8.5 hours; adults 7.9 hours). The most frequently reported (≥5% of participants) treatment-emergent adverse events in children included headache, upper abdominal pain and constipation, and in adolescents were headache, nausea, dizziness, and stomach discomfort. Multiple factors may have contributed to these observations, including a higher proportion of children (56%) who may have a lower activity of CYP2D6, resulting in reduced clearance of tramadol.

  7. Decreased diversion by doctor-shopping for a reformulated extended release oxycodone product (OxyContin).

    Science.gov (United States)

    Chilcoat, Howard D; Coplan, Paul M; Harikrishnan, Venkatesh; Alexander, Louis

    2016-08-01

    Doctor-shopping (obtaining prescriptions from multiple prescribers/pharmacies) for opioid analgesics produces a supply for diversion and abuse, and represents a major public health issue. An open cohort study assessed changes in doctor-shopping in the U.S. for a brand extended release (ER) oxycodone product (OxyContin) and comparator opioids before (July, 2009 to June, 2010) versus after (January, 2011 to June, 2013) introduction of reformulated brand ER oxycodone with abuse-deterrent properties, using IMS LRx longitudinal data covering >150 million patients and 65% of retail U.S. prescriptions. After its reformulation, the rate of doctor-shopping decreased 50% (for 2+ prescribers/3+ pharmacies) for brand ER oxycodone, but not for comparators. The largest decreases in rates occurred among young adults (73%), those paying with cash (61%) and those receiving the highest available dose (62%), with a 90% decrease when stratifying by all three characteristics. The magnitude of doctor-shopping reductions increased with increasing number of prescribers/pharmacies (e.g., 75% reduction for ≥2 prescribers/≥4 pharmacies). The rate of doctor-shopping for brand ER oxycodone decreased substantially after its reformulation, which did not occur for other prescription opioids. The largest reductions in doctor-shopping occurred with characteristics associated with higher abuse risk such as youth, cash payment and high dose, and with more specific thresholds of doctor-shopping. A higher prescriber and/or pharmacy threshold also increased the magnitude of the decrease, suggesting that it better captured the effect of the reformulation on actual doctor-shoppers. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson's Disease

    Science.gov (United States)

    Kim, Young Eun; Yang, Hui-Jun; Kim, Han-Joon

    2017-01-01

    This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson's disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson's disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov. PMID:28265478

  9. The role of paliperidone extended release for the treatment of bipolar disorder

    Directory of Open Access Journals (Sweden)

    Marino J

    2012-04-01

    Full Text Available Jehan Marino1, Clayton English2, Joshua Caballero1, Catherine Harrington11College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, 2College of Pharmacy, Albany College of Pharmacy and Health Sciences, Colchester, VT, USABackground: Bipolar disorder (BD is a chronic, relapsing, episodic mental illness associated with other psychiatric comorbidities. There is a substantial economic burden with BD, which makes it challenging to treat. The aim of this review is to evaluate the pharmacology, clinical efficacy, and safety data related to paliperidone extended release (ER for the treatment of BD.Methods: A literature search was performed from January 1966 through January 2012 using PreMEDLINE, MEDLINE, EMBASE, IPA, and ClinicalTrials.gov to identify articles in English regarding the pharmacology, clinical efficacy, and safety of paliperidone ER in acute mania or mixed episodes or in the maintenance treatment of BD I.Results: There are currently three published studies relating to the use of paliperidone ER for the treatment of BD. Two of these evaluated paliperidone ER as monotherapy for acute mania, while the other assessed its role as adjunct with a mood stabilizer.Conclusion: According to the limited available evidence, paliperidone at higher doses of ER 9–12 mg/day may be a safe and efficacious treatment option for acute episodes of mania in BD. A once-daily dose formulation may improve patient adherence to treatment; however, the cost of paliperidone ER, which is higher than that of generically available second-generation antipsychotics (such as olanzapine and risperidone, and a lack of alternative dosage forms (ie, liquid, intramuscular compared with other agents may limit its usefulness in the treatment of BD. The role of paliperidone ER as an adjunctive agent or for long-term use requires further investigation.Keywords: paliperidone ER, bipolar disorder, clinical efficacy, safety

  10. Film-coated matrix mini-tablets for the extended release of a water-soluble drug.

    Science.gov (United States)

    Mohamed, Faiezah A A; Roberts, Matthew; Seton, Linda; Ford, James L; Levina, Marina; Rajabi-Siahboomi, Ali R

    2015-04-01

    Extended release (ER) of water-soluble drugs from hydroxypropylmethylcellulose (HPMC) matrix mini-tablets (mini-matrices) is difficult to achieve due to the large surface area to volume ratio of the mini matrices. Therefore, the aims of this study were to control the release of a water-soluble drug (theophylline) from mini-matrices by applying ER ethylcellulose film coating (Surelease®), and to assess the effects of Surelease®:pore former (Opadry®) ratio and coating load on release rates. Mini-matrices containing 40%w/w HPMC K100M CR were coated with 100:0, 85:15, 80:20, 75:25 or 70:30 Surelease®:Opadry® to different coating weight gains (6-20%). Non-matrix mini-tablets were also produced and coated with 80:20 Surelease®:Opadry® to different coating weight gains. At low coating weight gains, nonmatrix mini-tablets released the entire drug within 0.5 h, while at high coating weight gains only a very small amount (<5%) of drug was released after 12 h. The gel formation of HPMC prevented disintegration of mini-matrices at low coating weight gains but contributed to rupture of the film even at high coating weight gains. As a result, drug release from mini-matrices was slower than that from nonmatrix mini-tablets at low coating weight gains, yet faster at high coating weight gains. An increase in the lag time of drug release from mini-matrices was observed as the concentration of Opadry® reduced or the coating weight gain increased. This study has demonstrated the possibility of extending the release of a water-soluble drug from HPMC mini-matrices by applying ER film coating with appropriate levels of pore former and coating weight gains to tailor the release rate.

  11. Assessing the Subjective and Physiological Effects of Intranasally Administered Crushed Extended-Release Morphine Formulations with and without a Sequestered Naltrexone Core in Recreational Opioid Users

    Directory of Open Access Journals (Sweden)

    Beatrice Setnik

    2013-01-01

    Full Text Available OBJECTIVE: To evaluate the pharmacodynamic (PD effects of morphine sulfate and naltrexone hydrochloride extended-release (MSN capsules compared with controlled-release morphine sulfate (MS and placebo when crushed and administered intranasally.

  12. Similar risk reduction of death of extended-release metoprolol once daily and immediate-release metoprolol twice daily during 5 years after myocardial infarction.

    Science.gov (United States)

    Herlitz, J; Dellborg, M; Karlson, B W; Lindqvist, J; Sandèn, W; Svensson, H; Sjölin, M; Wedel, H

    1999-04-01

    The pooled results from five placebo-controlled postinfarction studies with metoprolol have shown a significant reduction in total mortality. All five studies used immediate-release metoprolol twice daily. An extended-release formulation of metoprolol for once-daily use has since been developed. The aim of the present study was to compare the two different forms of metoprolol with regard to the risk reduction of death for 5 years postinfarction and to analyze whether treatment with the beta-blocker metoprolol is associated with a reduced mortality after the introduction of modern therapies such as thrombolysis, aspirin, and ACE inhibitors. All patients discharged after an acute myocardial infarction (AMI) from Sahlgrenska University Hospital (SU) during 1986-1987 (n = 740, Period I) and during 1990-1991 (n = 1446, Period II) from both SU and Ostra Hospital, Göteborg, Sweden, were included in the study. During Period I, 56% were prescribed immediate-release metoprolol compared with 61% prescribed extended-release metoprolol during Period II. Immediate-release metoprolol was not available for outpatient use during Period II. In a multivariate analysis, all variables significantly associated with either increased or decreased postinfarction mortality during Periods I and II (univariate analysis of patient characteristics, medical history, complications during the AMI medication at discharge) studied were with Cox's proportional hazards model. Treatment with immediate-release metoprolol was significantly associated with reduced mortality over 5 years during Period I (relative risk reduction for total mortality, -34%, P = 0.003; 95% CI for RR, 0.51-0.87), and treatment with extended-release metoprolol was significantly associated with reduced mortality during Period II (-34%, P metoprolol given once daily was associated with a similar risk reduction of death over 5 years as immediate-release metoprolol given twice daily. The data, furthermore, indicate that the beta

  13. Fluvoxamine monotherapy for psychotic depression: the potential role of sigma-1 receptors

    Directory of Open Access Journals (Sweden)

    Hashimoto Kenji

    2009-12-01

    Full Text Available Abstract Background Psychotic depression is a clinical subtype of major depressive disorder. A number of clinical studies have demonstrated the efficacy of the combination of an antidepressant (for example, a tricyclic antidepressant or selective serotonin reuptake inhibitor (SSRI and an atypical antipsychotic or electroconvulsive therapy in treating psychotic depression. In some cases, the clinician or patient may prefer to avoid antipsychotic drugs altogether because of the risk of extrapyramidal side effects (EPS in patients with psychotic depression treated with these drugs. Methods We report five cases where fluvoxamine monotherapy was effective in the patients with psychotic depression. Results The scores on the Hamilton Depression (HAM-D scale and the Brief Psychiatric Rating Scale (BPRS in the five patients with psychotic depression were reduced after fluvoxamine monotherapy. Conclusion Doctors should consider fluvoxamine monotherapy as an alternative approach in treating psychotic depression because it avoids the risk of EPS from antipsychotic drugs.

  14. Fluvoxamine for blonanserin-associated akathisia in patients with schizophrenia: report of five cases.

    Science.gov (United States)

    Furuse, Tsutomu; Hashimoto, Kenji

    2010-04-24

    Atypical antipsychotic drugs have been reported to cause fewer incidences of extrapyramidal side effects (EPS) than typical antipsychotic drugs, but adverse events such as akathisia have been observed even with atypical antipsychotic drugs. Although understanding of the pathophysiology of akathisia remains limited, it seems that a complex interaction of several neurotransmitter systems plays a role in its pathophysiology. The endoplasmic reticulum protein sigma-1 receptors have been shown to regulate a number of neurotransmitter systems in the brain. We report on five cases in which monotherapy of the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the akathisia of patients with schizophrenia treated with the new atypical antipsychotic drug blonanserin. The global score on the Barnes Akathisia Scale in five patients with schizophrenia treated with blonanserin rapidly decreased after fluvoxamine treatment. Doctors should consider that fluvoxamine may be an alternative approach in treating akathisia associated with atypical antipsychotic drugs.

  15. Fluvoxamine for blonanserin-associated akathisia in patients with schizophrenia: report of five cases

    Directory of Open Access Journals (Sweden)

    Hashimoto Kenji

    2010-04-01

    Full Text Available Abstract Background Atypical antipsychotic drugs have been reported to cause fewer incidences of extrapyramidal side effects (EPS than typical antipsychotic drugs, but adverse events such as akathisia have been observed even with atypical antipsychotic drugs. Although understanding of the pathophysiology of akathisia remains limited, it seems that a complex interaction of several neurotransmitter systems plays a role in its pathophysiology. The endoplasmic reticulum protein sigma-1 receptors have been shown to regulate a number of neurotransmitter systems in the brain. Methods We report on five cases in which monotherapy of the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the akathisia of patients with schizophrenia treated with the new atypical antipsychotic drug blonanserin. Results The global score on the Barnes Akathisia Scale in five patients with schizophrenia treated with blonanserin rapidly decreased after fluvoxamine treatment. Conclusion Doctors should consider that fluvoxamine may be an alternative approach in treating akathisia associated with atypical antipsychotic drugs.

  16. Cost-effectiveness of lurasidone vs quetiapine extended-release (XR) in patients with bipolar depression.

    Science.gov (United States)

    Rajagopalan, Krithika; Meyer, Kellie; O'Day, Ken; Denno, Melissa; Loebel, Antony

    2015-01-01

    Bipolar disorder imposes a high economic burden on patients and society. Lurasidone and quetiapine extended-release (XR) are atypical antipsychotic agents indicated for monotherapy treatment of bipolar depression. Lurasidone is also indicated as adjunctive therapy with lithium or valproate for depressive episodes associated with bipolar disorder. The objective of this analysis was to estimate the cost-effectiveness of lurasidone and quetiapine XR in patients with bipolar depression. A cost-effectiveness model was developed to compare lurasidone to quetiapine XR. The model was based on a US third-party payer perspective over a 3-month time horizon. The effectiveness measure in the model was the percentage of patients achieving remission (Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≤12 by weeks 6-8). The comparison of remission rates was made through an adjusted indirect treatment comparison of lurasidone and quetiapine XR pivotal trials using placebo as the common comparator. Resource utilization for remission vs no remission was estimated from published expert panel data, and resource costs were obtained from a retrospective database study of bipolar I depression patients. Drug costs were estimated using the mean dose from clinical trials and wholesale acquisition costs. Over the 3-month model time period, lurasidone and quetiapine XR patients, respectively, had similar mean numbers of emergency department visits (0.48 vs 0.50), inpatient days (2.1 vs 2.2), and office visits (9.3 vs 9.6). More lurasidone than quetiapine XR patients achieved remission (52.0% vs 43.2%) with slightly higher total costs ($4982 vs $4676), resulting in an incremental cost-effectiveness ratio of $3474 per remission. The probabilistic sensitivity analysis showed lurasidone had an 86% probability of being cost-effective compared to quetiapine XR at a willingness-to-pay threshold of $10,000 per remission. Lurasidone may be a cost-effective option when compared to

  17. Extended-release niacin/laropiprant improves endothelial function in patients after myocardial infarction.

    Science.gov (United States)

    Bregar, Urska; Jug, Borut; Keber, Irena; Cevc, Matija; Sebestjen, Miran

    2014-05-01

    Raising high-density lipoprotein cholesterol (HDL-C) is an important strategy for reducing residual cardiovascular risk. In the present study, we sought to assess the effect of extended-release niacin/laropiprant on endothelial function in patients after a myocardial infarction with target low-density lipoprotein cholesterol (LDL-C). In this double-blind, placebo-controlled trial, 63 men (35-60 years of age) after a myocardial infarction were randomized to either niacin/laropiprant (1000/20 mg daily for 4 weeks and 2000/40 mg daily thereafter) or placebo. Flow-mediated dilation (FMD) and nitroglycerin-induced (GTN) dilation of the brachial artery, total cholesterol (TC), LDL-C, HDL-C, triglycerides (TG), lipoprotein(a) [Lp(a)], and apolipoprotein (Apo) A1/B were measured at baseline and after 12 weeks of intervention. FMD significantly increased (from 3.9 ± 5.1 to 9.8 ± 4.4%, p niacin/laropiprant group, but not in the placebo group (4.6 ± 4.4 to 6.1 ± 4.4%, p = 0.16) (p = 0.02 for comparison of interventions). GTN dilation also increased in the niacin/laropiprant group (from 12.5 ± 6.1 to 16.7 ± 4.8%, p = 0.02), but not in the placebo group (13.4 ± 5.0 to 15.1 ± 5.2%, p = 0.18), (p = 0.60 for comparison of interventions). Niacin/laropiprant reduced TC and LDL-C (p = 0.05 for both) and increased HDL-C (p niacin/laropiprant group, with no difference in the placebo group. ApoA1 did not change in either of the groups (p = 0.13; p = 0.26). FMD and GTN dilation improvements did not correlate with changes in the lipid profile. Niacin/laropiprant improves endothelium-dependent and endothelium-independent dilation of the brachial artery. This improvement does not correlate with changes in lipid parameters.

  18. Efficacy of fesoterodine compared with extended-release tolterodine in men and women with overactive bladder.

    Science.gov (United States)

    Ginsberg, David; Schneider, Tim; Kelleher, Con; Van Kerrebroeck, Philip; Swift, Steven; Creanga, Dana; Martire, Diane L

    2013-08-01

    To assess the efficacy of fesoterodine 8 mg vs extended-release (ER) tolterodine 4 mg for overactive bladder (OAB) symptoms in terms of patient-reported outcomes in women and in men. Pooled data from two 12-week, randomized, double-blind, double-dummy studies were analysed. Participants eligible for the studies were ≥18 years old, had self-reported OAB symptoms for ≥3 months in 3-day baseline diaries and had ≥8 micturitions and ≥1 urgency urinary incontinence (UUI) episode per 24 h. Individuals were randomized to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks), ER tolterodine (4 mg), or placebo. Changes from baseline in 3-day bladder diary variables and scores from the Patient Perception of Bladder Condition (PPBC), Urgency Perception Scale (UPS), and Overactive Bladder Questionnaire (OAB-q), were assessed, as was the 'diary-dry' rate (the proportion of subjects with >0 UUI episodes according to baseline diary and no UUI episodes according to post-baseline diary). The primary endpoint was the change from baseline to week 12 in UUI episodes. At week 12, women showed significantly greater improvement with fesoterodine 8 mg (n = 1374) than with ER tolterodine 4 mg (n = 1382) and placebo (n = 679) in UUI episodes (primary endpoint), micturition frequency, urgency episodes, and all other diary endpoints (except nocturnal micturitions versus ER tolterodine), and also in scores on the PPBC, UPS, and all OAB-q scales and domains (all P fesoterodine (63%) than with tolterodine (57%; P = 0.002) or placebo (48%; P fesoterodine 8 mg (n = 265) than with ER tolterodine (n = 275) for severe urgency and the OAB-q Symptom Bother domain and were also significantly greater with fesoterodine than with placebo (n = 133) for micturition frequency, urgency episodes, severe urgency episodes, PPBC responses and scores on all OAB-q scales and domains at week 12 (all P fesoterodine, 29%; ER tolterodine, 15%; placebo, 6%; men: fesoterodine, 21%; ER

  19. Effects of paliperidone extended release on hostility among Thai patients with schizophrenia

    Science.gov (United States)

    Jariyavilas, Apichat; Thavichachart, Nuntika; Kongsakon, Ronnachai; Chantakarn, Sunanta; Arunpongpaisal, Suwanna; Chantarasak, Vasu; Jaroensook, Piyadit; Kittiwattanagul, Khanogwan; Nerapusee, Osot

    2017-01-01

    Objective This open-label prospective study investigated the effects of paliperidone extended release (ER) on hostility in Thai patients with schizophrenia. Background Patients diagnosed with schizophrenia may be hostile or exhibit aggressive behavior, which can occasion their admission to psychiatric hospital. Antipsychotic medications are often used to treat hostility and aggression in such patients. Paliperidone ER is effective and well tolerated in the treatment of schizophrenia. However, there are no data available for paliperidone ER with regard to its efficacy on hostility and aggression among Thai patients. This study was a part of the PERFEcT study, a 6-month, open-label, multicenter, multicountry, prospective trial to explore the safety, efficacy, and functionality of paliperidone ER tablets. The current study included only the data obtained from Thai participants. Materials and methods Flexible dosing of paliperidone ER in a range of 3–12 mg/day was used, allowing investigators to adjust the dosage of each subject individually. The 199 Thai patients had a stable Clinical Global Impression – severity score before enrollment. Demographic data were collected at enrollment, and assessments took place at 1, 2, 3, and 6 months postbaseline. The Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale were used to evaluate efficacy. In this analysis, we report the findings for the specific PANSS factor P7 (hostility) and the PSP subscale disturbing and aggressive behavior. Data were analyzed using paired t-test method to investigate changes in mean PANSS and PSP total and subscale scores. The significance level was set at P<0.05. Results From a total of 199 Thai patients, 148 patients (74.4%) participated in all visits. There was a significant reduction in mean scores for all total PANSS measures from 1 month onward compared with baseline, as well as ongoing significant reductions in scores from visit to visit. There was

  20. Healthcare utilization in adults with opioid dependence receiving extended release naltrexone compared to treatment as usual.

    Science.gov (United States)

    Soares, William E; Wilson, Donna; Rathlev, Niels; Lee, Joshua D; Gordon, Michael; Nunes, Edward V; O'Brien, Charles P; Friedmann, Peter D

    2017-05-12

    Opioid use disorders have reached epidemic proportions, with overdose now the leading cause of accidental death in the United States. Extended release naltrexone (XR-NTX) has emerged as a medication treatment that reduces opioid use and craving. However, the effect of XR-NTX therapy on acute healthcare utilization, including emergency department visits and inpatient hospitalizations, remains uncertain. The objective of the current study is to evaluate hospital-based healthcare resource utilization in adults involved in the criminal justice system with a history of opioid use disorder randomized to XR-NTX therapy compared with treatment as usual (TAU) during a 6-month treatment phase and 12months post-treatment follow up. This retrospective exploratory analysis uses data collected in a published randomized trial. Comparisons of the number of emergency department visits and hospital admissions (for drug detox, psychiatric care and other medical reasons) were performed using chi square tests for any admission and negative binomial models for number of admissions. Of the 308 participants randomized, 96% had utilization data (76% complete 6months, 67% complete follow up). No significant differences were seen in overall healthcare utilization (IRR=0.88, 95%CI 0.63-1.23, p=0.45), or substance use-related drug detox hospitalizations (IRR=0.83, 95%CI 0.32-2.16, p=0.71). Despite having more participants report chronic medical problems at baseline (43% vs. 32%, p=0.05), those receiving XR-NTX generally experienced equivalent or lower rates of healthcare utilization compared to TAU. The XR-NTX group had significantly lower medical/surgical related hospital admissions (IRR=0.55, 95%CI 0.30-1.00, p=0.05) during the course of the entire study. XR-NTX did not significantly increase rates of healthcare utilization compared to TAU. Provider concerns regarding healthcare utilization should not preclude the consideration of XR-NTX as therapy for opioid use disorders. Copyright © 2017

  1. Acute treatment with fluvoxamine elevates rat brain serotonin synthesis in some terminal regions: An autoradiographic study

    Science.gov (United States)

    Muck-Seler, Dorotea; Pivac, Nela; Diksic, Mirko

    2013-01-01

    Introduction A considerable body of evidence indicates the involvement of the neurotransmitter serotonin (5-HT) in the pathogenesis and treatment of depression. Methods The acute effect of fluvoxamine, on 5-HT synthesis rates was investigated in rat brain regions, using α-14C-methyl-L-tryptophan as a tracer. Fluvoxamine (25 mg/kg) and saline (control) were injected intraperitoneally, one hour before the injection of the tracer (30 μCi). Results There was no significant effect of fluvoxamine on plasma free tryptophan. After Benjamini–Hochberg False Discovery Rate correction, a significant decrease in the 5-HT synthesis rate in the fluvoxamine treated rats, was found in the raphe magnus (−32%), but not in the median (−14%) and dorsal (−3%) raphe nuclei. In the regions with serotonergic axon terminals, significant increases in synthesis rates were observed in the dorsal (+41%) and ventral (+43%) hippocampus, visual (+38%), auditory (+65%) and parietal (+37%) cortex, and the substantia nigra pars compacta (+56%). There were no significant changes in the 5-HT synthesis rates in the median (+11%) and lateral (+24%) part of the caudate-putamen, nucleus accumbens (+5%), VTA (+16%) or frontal cortex (+ 6%). Conclusions The data show that the acute administration of fluvoxamine affects 5-HT synthesis rates in a regionally specific pattern, with a general elevation of the synthesis in the terminal regions and a reduction in some cell body structures. The reasons for the regional specific effect of fluvoxamine on 5-HT synthesis are unclear, but may be mediated by the presynaptic serotonergic autoreceptors. PMID:22560971

  2. Critical appraisal of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia.

    Science.gov (United States)

    Hussein, Ayman A; Nicholls, Stephen J

    2010-04-15

    Niacin is a B-complex vitamin which has been used for decades for the management of mixed dyslipidemias and primary hypercholesterolemia. It decreases the risk of cardiovascular events either when used as a monotherapy or in combination with other lipid lowering medications. However, a major limitation to its use is niacin-induced flushing occurring even with the extended-release formulations. Laropiprant, a selective prostaglandin-2 receptor inhibitor, specifically targets the cascade of events causing the flushing. It has been recently used in combination with extended-release niacin. This article will review the early experience with this combination with focus on efficacy, safety, tolerability and current place in therapy. Early data are promising and suggest that more patients in clinical practice will benefit from niacin combined with laropiprant. Ongoing clinical trials will provide a better insight on the long-term safety of the drug and its efficacy for reducing cardiovascular events.

  3. Gender differences in pharmacokinetics of a combination tablet of niacin extended-release/simvastatin in healthy Chinese volunteers.

    Science.gov (United States)

    Wang, Xiao-lin; Liu, Man; Yang, Man; Zhang, Ya-nan; Zhang, Dan; Zhang, Li-na; Han, Jing; Liu, Hui-chen

    2014-12-01

    The gender differences in pharmacokinetics of a combination tablet of niacin extended-release/simvastatin were evaluated in healthy Chinese volunteers. Thirty-six healthy male and female volunteers were enrolled in the study receiving a single oral dose of niacin extended-release/simvastatin 1,000/20 mg. The results indicated that the systemic exposure of simvastatin hydroxy acid and the total urine excretion of niacin were significantly higher for females compared with those for males, and the T max of niacin in plasma was significantly shorter for males than that for females. There were no significant differences in the systemic exposure of simvastatin, niacin, and NUA in plasma between males and females.

  4. Disulfiram-loaded immediate and extended release vaginal tablets for the localised treatment of cervical cancer.

    Science.gov (United States)

    Baffoe, Clara S; Nguyen, Nhi; Boyd, Peter; Wang, Weiguang; Morris, Mark; McConville, Christopher

    2015-02-01

    To develop and manufacture both immediate and sustained release vaginal tablets containing the anticancer drug disulfiram, which has the potential to be used as a non-invasive treatment for cervical cancer. Disulfiram-loaded vaginal tablets were manufactured at pilot scale using the direct compression method. These tablets were tested in accordance with the European Pharmacopeia testing of solid dosage form guidelines. They were also tested using a biorelevant dissolution method as well as a dual-chambered release model designed to better mimic the dynamic nature of the vaginal vault. We have developed both immediate and sustained release vaginal tablets, which when manufactured at pilot scale are within the limits set by the European Pharmacopeia for the testing of solid dosage forms. Furthermore, these tablets are capable of releasing disulfiram in vitro using the dual-chambered release model at levels 25,000 times and 35,000 times greater than its IC50 concentration for the HeLa cervical cancer cell line. The successful pilot manufacture and testing of both the immediate and sustained release disulfiram-loaded vaginal tablets warrant further investigation, using an in-vivo model, to assess their potential for use as a non-invasive treatment option for cervical cancer. © 2014 Royal Pharmaceutical Society.

  5. Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing.

    Science.gov (United States)

    Skowyra, Justyna; Pietrzak, Katarzyna; Alhnan, Mohamed A

    2015-02-20

    Rapid and reliable tailoring of the dose of controlled release tablets to suit an individual patient is a major challenge for personalized medicine. The aim of this work was to investigate the feasibility of using a fused deposition modelling (FDM) based 3D printer to fabricate extended release tablet using prednisolone loaded poly(vinyl alcohol) (PVA) filaments and to control its dose. Prednisolone was loaded into a PVA-based (1.75 mm) filament at approximately 1.9% w/w via incubation in a saturated methanolic solution of prednisolone. The physical form of the drug was assessed using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). Dose accuracy and in vitro drug release patterns were assessed using HPLC and pH change flow-through dissolution test. Prednisolone loaded PVA filament demonstrated an ability to be fabricated into regular ellipse-shaped solid tablets using the FDM-based 3D printer. It was possible to control the mass of printed tablet through manipulating the volume of the design (R(2) = 0.9983). On printing tablets with target drug contents of 2, 3, 4, 5, 7.5 and 10mg, a good correlation between target and achieved dose was obtained (R(2) = 0.9904) with a dose accuracy range of 88.7-107%. Thermal analysis and XRPD indicated that the majority of prednisolone existed in amorphous form within the tablets. In vitro drug release from 3D printed tablets was extended up to 24h. FDM based 3D printing is a promising method to produce and control the dose of extended release tablets, providing a highly adjustable, affordable, minimally sized, digitally controlled platform for producing patient-tailored medicines. Copyright © 2015. Published by Elsevier B.V.

  6. Efficacy of Tramadol Extended-Release for Opioid Withdrawal: A Randomized Clinical Trial.

    Science.gov (United States)

    Dunn, Kelly E; Tompkins, D Andrew; Bigelow, George E; Strain, Eric C

    2017-09-01

    Opioid use disorder (OUD) is a significant public health problem. Supervised withdrawal (ie, detoxification) from opioids using clonidine or buprenorphine hydrochloride is a widely used treatment. To evaluate whether tramadol hydrochloride extended-release (ER), an approved analgesic with opioid and nonopioid mechanisms of action and low abuse potential, is effective for use in supervised withdrawal settings. A randomized clinical trial was conducted in a residential research setting with 103 participants with OUD. Participants' treatment was stabilized with morphine, 30 mg, administered subcutaneously 4 times daily. A 7-day taper using clonidine (n = 36), tramadol ER (n = 36), or buprenorphine (n = 31) was then instituted, and patients were crossed-over to double-blind placebo during a post-taper period. The study was conducted from October 25, 2010, to June 23, 2015. Retention, withdrawal symptom management, concomitant medication utilization, and naltrexone induction. Results were analyzed over time and using area under the curve for the intention-to-treat and completer groups. Of the 103 participants, 88 (85.4%) were men and 43 (41.7%) were white; mean (SD) age was 28.9 (10.4) years. Buprenorphine participants (28 [90.3%]) were significantly more likely to be retained at the end of the taper compared with clonidine participants (22 [61.1%]); tramadol ER retention was intermediate and did not differ significantly from that of the other groups (26 [72.2%]; χ2 = 8.5, P = .01). Time-course analyses of withdrawal revealed significant effects of phase (taper, post taper) for the Clinical Opiate Withdrawal Scale (COWS) score (taper mean, 5.19 [SE, .26]; post-taper mean, 3.97 [SE, .23]; F2,170 = 3.6, P = .03) and Subjective Opiate Withdrawal Scale (SOWS) score (taper mean,8.81 [SE, .40]; post-taper mean, 4.14 [SE, .30]; F2,170 = 15.7, P tramadol ER (taper mean, 7.4; post-taper mean, 2.8; P = .03), but not buprenorphine (taper mean

  7. Effects of paliperidone extended release on hostility among Thai patients with schizophrenia

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    Jariyavilas A

    2017-01-01

    Full Text Available Apichat Jariyavilas,1 Nuntika Thavichachart,2 Ronnachai Kongsakon,3 Sunanta Chantakarn,4 Suwanna Arunpongpaisal,5 Vasu Chantarasak,6 Piyadit Jaroensook,7 Khanogwan Kittiwattanagul,8 Osot Nerapusee9 1Srithanya Hospital, Department of Mental Health, Ministry of Public Health, Bangkok, 2Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, 3Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Bangkok, 4Department of Psychiatry, Faculty of Medicine, Siriraj Hospital, Bangkok, 5Department of Psychiatry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 6Somdetchaopraya Institute of Psychiatry, Bangkok, 7Prasrimahabhodhi Hospital, Ubon Ratchathani, 8Khon Kaen Rajanagarindra Psychiatric Hospital, Khon Kaen, 9Medical Affairs, Janssen-Cilag, Bangkok, Thailand Objective: This open-label prospective study investigated the effects of paliperidone extended release (ER on hostility in Thai patients with schizophrenia. Background: Patients diagnosed with schizophrenia may be hostile or exhibit aggressive behavior, which can occasion their admission to psychiatric hospital. Antipsychotic medications are often used to treat hostility and aggression in such patients. Paliperidone ER is effective and well tolerated in the treatment of schizophrenia. However, there are no data available for paliperidone ER with regard to its efficacy on hostility and aggression among Thai patients. This study was a part of the PERFEcT study, a 6-month, open-label, multicenter, multicountry, prospective trial to explore the safety, efficacy, and functionality of paliperidone ER tablets. The current study included only the data obtained from Thai participants. Materials and methods: Flexible dosing of paliperidone ER in a range of 3–12 mg/day was used, allowing investigators to adjust the dosage of each subject individually. The 199 Thai patients had a stable Clinical Global Impression – severity score before enrollment. Demographic

  8. Rikkunshi-to attenuates adverse gastrointestinal symptoms induced by fluvoxamine

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    Kodama Naoki

    2007-11-01

    Full Text Available Abstract Background Upper gastrointestinal (GI symptoms such as nausea and vomiting are common adverse events associated with selective serotonin reuptake inhibitors (SSRIs, and may result in discontinuation of drug therapy in patients with depressive disorder. Rikkunshi-to (formulation TJ-43, a traditional herbal medicine, has been reported to improve upper GI symptoms and comorbid depressive symptoms in patients with functional dyspepsia. The aim of the present study was to determine if TJ-43 reduces GI symptoms and potentiates an antidepressant effect in a randomized controlled study of depressed patients treated with fluvoxamine (FLV. Methods Fifty patients with depressive disorder (19–78 years, mean age 40.2 years were treated with FLV (n = 25 or FLV in combination with TJ-43 (FLV+TJ-43 (n = 25 for eight weeks. The following parameters of the two groups were compared: The number of patients who complained of adverse events and their symptoms; GI symptoms quality of life (QOL score, assessed by the Gastrointestinal Symptom Rating Scale (GSRS, Japanese edition, before and two weeks after beginning treatment; and depressive symptoms assessed by the Self-Rating Depression Scale (SDS, before and 2, 4, and 8 weeks after beginning treatment. Results The number of patients who complained of adverse events in the FLV+TJ-43 group (n = 6 was significantly lower than the number complaining in the FLV group (n = 13 (P P Conclusion This study suggests that Rikkunshi-to reduces FLV-induced adverse events, especially nausea, and improves QOL related to GI symptoms without affecting the antidepressant effect of FLV.

  9. Zolpidem extended-release improves sleep and next-day symptoms in comorbid insomnia and generalized anxiety disorder.

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    Fava, Maurizio; Asnis, Gregory M; Shrivastava, Ram; Lydiard, Bruce; Bastani, Bijan; Sheehan, David; Roth, Thomas

    2009-06-01

    A multicenter, double-blind, parallel-group study was designed to assess the efficacy and safety of zolpidem extended-release coadministered with escitalopram in patients with insomnia and comorbid generalized anxiety disorder. Patients (N = 383) received open-label escitalopram 10 mg/d and were randomized to either adjunct zolpidem extended-release 12.5 mg or placebo. The primary efficacy measure was change from baseline to week 8 in subjective total sleep time. Secondary efficacy measures included subjective sleep onset latency, number of awakenings, wake time after sleep onset, sleep quality, the Hamilton Rating Scale for Anxiety, the Beck Anxiety Inventory, the Sleep Impact Scale, the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire, and the Sheehan Disability Scale. The last-observation-carried-forward method was used to impute missing values for most efficacy measures. Safety was monitored at each visit. At week 8 and all time points, there was a significant improvement in the zolpidem extended-release/escitalopram group compared with placebo/escitalopram for total sleep time (P escitalopram, compared with placebo/escitalopram, significantly improved insomnia and sleep-related next-day symptoms, but not anxiety symptoms, in patients with comorbid insomnia and generalized anxiety disorder.

  10. Extended latanoprost release from commercial contact lenses: in vitro studies using corneal models.

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    Saman Mohammadi

    Full Text Available In this study, we compared, for the first time, the release of a 432 kDa prostaglandin F2a analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution (131 μg = ml solution in phosphate buffered saline. The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC, and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment whereby, after 48 hours, between 4 to 6 μg of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 μg, was released, (p <0:001. The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.

  11. The opposite effects of fluvoxamine and sertraline in the treatment of psychotic major depression: a case report

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    Kitagaki Tetsuno

    2010-05-01

    Full Text Available Abstract Background Psychotic major depression is a clinical subtype of major depressive disorder. A number of clinical studies have demonstrated the efficacy of the combination of an antidepressant (for example, a tricyclic antidepressant or selective serotonin reuptake inhibitor (SSRI and an atypical antipsychotic or electroconvulsive therapy (ECT in treating psychotic major depression. In several studies, monotherapy of SSRIs such as fluvoxamine has been shown to be effective in the treatment of psychotic major depression. Methods We report on a 36-year-old Japanese woman in whom fluvoxamine (a SSRI with sigma-1 receptor agonist and sertraline (a SSRI with sigma-1 receptor antagonist showed the opposite effects on psychotic symptoms in the treatment of psychotic major depression. Results Symptoms of depression and psychosis in the patient who was non-respondent to antipsychotic drugs improved after fluvoxamine monotherapy. At 3 years later, a switch to sertraline from fluvoxamine dramatically worsened the psychotic symptoms in the patient. Then, a switch back to fluvoxamine from sertraline improved these symptoms 1 week after fluvoxamine treatment. Conclusion Doctors should consider the monotherapy of sigma-1 receptor agonist fluvoxamine as an alternative approach to treating psychotic major depression.

  12. Design, Development and Characterization of Extended Release Multiunit Particulate System of Anti-Inflammatory Drug

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    Dhiren Daslaniya

    2009-07-01

    Full Text Available Multi unit particulate system has long been employed to improve the bioavailability of drugs. Mesalamine pellets were prepared by Coating drug solution on sugar sphere followed by various functional coating. The influence of rate controlling membrane made up of Eudragit RSPO and Eudragit RLPO in combination with delay release polymer coating with Eudragit L100 in different proportions on drug release kinetics was studied. Pellets were for the various parameter like Physical characteristics, assay and in-vitro dissolution profile. The study confirmed that mesalamine can be delivered by multi unit particulate system into lower part of intestine. Optimized formulations were evaluated for In-vitro release profile. The optimized formula was stable at accelerated storage condition 40°C / 75 % RH. Prepared Pellets can be used in the treatment of the ulcerative colitis.

  13. Pilot Study: Fluvoxamine Treatment for Depression and Anxiety Disorders in Children and Adolescents with Cancer

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    Gothelf, Doron; Rubinstein, Maly; Shemesh, Eyal; Miller, Orit; Farbstein, Ilana; Klein, Anat; Weizman, Abraham; Apter, Alan; Yaniv, Isaac

    2005-01-01

    Objective: To evaluate the safety, tolerability, and benefit of fluvoxamine for the treatment of major depressive disorder or anxiety disorders in children and adolescents with cancer. Method: The study was conducted from 2001 to 2004 at a pediatric hematology-oncology center. Fifteen children and adolescents with cancer were treated with…

  14. Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus

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    Levy Juliana

    2010-03-01

    Full Text Available Abstract Aims To determine prospectively the efficacy, tolerability and patient satisfaction of an extended release formulation of metformin (metformin XR in hospital based outpatients with type 2 diabetes mellitus currently treated with standard metformin. Methods Patients on immediate release standard metformin either alone or combined with other oral agents were switched to extended release metformin XR 500 mg tablets and titrated to a maximum dose of 2000 mg/day Measurements to include glucose and lipid control, blood pressure, body weight, waist circumference, C-reactive protein, adverse events and patient satisfaction were recorded at baseline, three and six months. Results Complete data were obtained for 35 of the 61 patients enrolled to the study. At three and six months no changes were reported for any of the cardiovascular risk factors except for lipids where there was a modest rise in plasma triglycerides. These effects were achieved with a reduced dose of metformin XR compared to pre-study dosing with standard metformin (1500 mg +/- 402 vs 1861 +/- 711 p = 0.004. A total of 77% of patients were free of gastrointestinal side effects and 83% of patients stated a preference for metformin XR at the end of the study. Ghost tablets were reported in the faeces by the majority of the patients (54.1%. Conclusions Patients switched to extended release metformin XR derived the same clinical and metabolic benefits as for standard metformin but with reduced dosage, fewer gastrointestinal side effects and a greater sense of well being and satisfaction on medication.

  15. Assessment of pharmacokinetics and pharmacodynamic effects related to abuse potential of a unique oral osmotic-controlled extended-release methylphenidate formulation in humans.

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    Parasrampuria, Dolly A; Schoedel, Kerri A; Schuller, Reinhard; Gu, Joan; Ciccone, Patrick; Silber, Steven A; Sellers, Edward M

    2007-12-01

    This was a double-blind, placebo-controlled, randomized, 5-period crossover study in 49 healthy subjects with a history of light (occasional) recreational stimulant use, to evaluate the abuse-related subjective effects of oral osmotic-controlled extended-release methylphenidate with comparable doses of immediate-release methylphenidate. Healthy subjects with a history of light recreational stimulant use were enrolled in the study if they demonstrated a positive response to a 20-mg dose of d-amphetamine and a negative placebo response. Enrolled subjects received single doses of placebo, 54 and 108 mg osmotic-controlled extended-release methylphenidate, and 50 and 90 mg immediate-release methylphenidate. For each treatment, pharmacokinetics, pharmacodynamics, and safety were assessed for 24 hours. Subjective data were collected through standard questionnaires and visual analog scales for positive, stimulant, negative, and other effects. Immediate-release and osmotic-controlled extended-release methylphenidate produced expected plasma concentration-time profiles of d-methylphenidate. Both doses of immediate-release methylphenidate (50 and 90 mg) produced statistically significantly higher subjective effects (eg, positive, stimulant) with respect to placebo for all measures. The higher osmotic-controlled extended-release methylphenidate dose of 108 mg also produced statistically significant differences from placebo for most measures. However, the most commonly prescribed therapeutic dose of osmotic-controlled extended-release methylphenidate (54 mg) did not produce significant differences from placebo for most measures. In addition, for comparable dose levels, osmotic-controlled extended-release methylphenidate produced lower positive and stimulant subjective effects than immediate-release methylphenidate, and low-dose immediate-release methylphenidate (50 mg) produced greater subjective effects than high-dose osmotic-controlled extended-release methylphenidate, with

  16. Plasma levels of catecholamine metabolites predict the response to sulpiride or fluvoxamine in major depression.

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    Ueda, N; Yoshimura, R; Shinkai, K; Nakamura, J

    2002-09-01

    We investigated the relationships between the changes in plasma catecholamine metabolites obtained from depressed patients before and after administration of sulpiride, a benzamide compound, or fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), and between clinical responses to treatment with each of these drugs. Responders to sulpiride had significantly lower plasma homovanillic acid (pHVA) levels before administration of sulpiride than did non-responders or controls (responders: 4.5 +/- 3.1 ng/ml, non-responders: 11.1 +/- 5.9 ng/ml, controls: 10.9 +/- 5.3 ng/ml). Positive relationships were observed between changes in pHVA levels and improvement rates in the 17-item Hamilton Depression Rating Scale (Ham-D). In contrast, responders to fluvoxamine had significantly higher plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels before administration of fluvoxamine than did non-responders or controls (responders: 8.5 +/- 1.8 ng/ml, non-responders: 5.9 +/- 2.I ng/ml, controls: 5.2 +/- 2.9 ng/ml). Negative relationships were observed between changes in pMHPG levels and improvement rates in Ham-D. These results suggest that lower pretreatment pHVA levels and higher pretreatment levels of pMHPG might be predictors of response to sulpiride and fluvoxamine, respectively, and that sulpiride might produce a functional increase in the dopaminergic system, resulting in improvement in some depressive symptoms; fluvoxamine, on the other hand, might produce a functional decrease in the noradrenergic system via serotonergic neurons, resulting in improvement of those symptoms.

  17. Prevention of organ rejection in renal and liver transplantation with extended release tacrolimus

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    Reschen ME

    2014-09-01

    Full Text Available Michael E Reschen, Christopher A O’Callaghan Henry Wellcome Building, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom Abstract: Tacrolimus is the key immunosuppressant used to prevent allograft rejection in kidney and liver transplant recipients. Despite the efficacy of tacrolimus and adjunctive immunosuppressants, a substantial number of patients experience episodes of acute rejection and late graft loss. Nonadherence is an etiological factor in both acute rejection and graft loss. In 2007, a prolonged release version of tacrolimus became available that allows once daily administration, thus halving the pill burden compared to the standard twice-daily tacrolimus. An increasing number of studies in de novo transplantation and in treatment conversion have evaluated the pharmacokinetic profile, efficacy, and safety of prolonged-release tacrolimus. We have reviewed the literature on the use of prolonged-release tacrolimus and hope that this will be of value in the design of protocols for transplant immunosuppression.Keywords: immunosuppression, kidney, hepatic, allograft, adherence

  18. Controlled extended octenidine release from a bacterial nanocellulose/Poloxamer hybrid system.

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    Alkhatib, Y; Dewaldt, M; Moritz, S; Nitzsche, R; Kralisch, D; Fischer, D

    2017-03-01

    Although bacterial nanocellulose (BNC) has been widely investigated in the last 10years as drug delivery system, up to now no long-term controlled release of drugs could be realized. Therefore, the aim of the present work was the development of a BNC-based drug delivery system that provides prolonged retention time for the antiseptic octenidine up to one week with improved mechanical and antimicrobial properties as well as a high biocompatibility. BNC was modified by incorporation of differently concentrated Poloxamers 338 and 407 as micelles and gels that were extensively investigated regarding size, surface charge, and dynamic viscosity. Depending on type and concentration of the Poloxamer, a retarded octenidine release up to one week could be accomplished. Additionally, superior material properties such as high compression stability and water binding could be achieved. The antimicrobial activity of octenidine against Staphylococcus aureus and Pseudomonas aeruginosa was not changed by the use of Poloxamers. Excellent biocompatibility of the Poloxamer loaded BNC could be demonstrated after local administration in a shell-less hen's egg model. In conclusion, a long-term delivery system consisting of BNC and Poloxamer could be developed for octenidine as a ready-to-use system e.g. for long-term dermal wound treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Bacteriophage and impurity carryover and total organic carbon release during extended protein A chromatography.

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    Lute, Scott; Brorson, Kurt

    2009-05-01

    In the biopharmaceutical industry, column chromatography residuals are routinely assessed by the direct measurement of mock eluates. In this study, we evaluated virus and other impurity carryover between protein A cycles and the feasibility of using a total organic carbon (TOC) analyzer to monitor for column impurity leakage as a correlate for actual measured carryover in mock eluates. Commercial process intermediates were used in scaled down studies of two protein A media, ProSep A (Millipore, Bedford, MA, USA) and MabSelect SuRe (GE Healthcare, Uppsala, Sweden). The chromatography system was programmed to run up to 200 normal load/elution cycles with periodic blank cycles to measure protein and phage carryover, and water flush cycles to measure TOC release. Sustained phage carryover was evident in each study. Carryover and TOC release was lowest in the case where cleaning was most stringent (50 mM NaOH/0.5 M Na(2)SO(4) with MabSelect SuRe). The TOC analysis at this time does not appear to be a viable practical means of measuring impurity carryover; direct measurements in mock eluates appears to be more predictive of column performance.

  20. Lipids bearing extruded-spheronized pellets for extended release of poorly soluble antiemetic agent-Meclizine HCl.

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    Qazi, Faaiza; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Nasiri, Muhammad Iqbal; Ahmed, Kamran; Ahmad, Mansoor

    2017-04-12

    Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated. Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol(®)), Glyceryl palmitostearate (Precirol(®)), Glyceryl behenate (Compritol(®)) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found. Sphericity indicated by shape factor (eR) varied with type and concentration of lipids: Geleol(®) (eR = 0.891-0.997), Precirol(®) (eR = 0.611-0.743), Compritol(®) (eR = 0.665-0.729) and Carnauba wax (eR = 0.499-0.551). Highly spherical pellets were obtained with Geleol(®) (Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol(®) and Compritol(®), (ii) Geleol(®) and Carnauba wax and (iii) Geleol(®), Compritol(®) and Carnauba wax. Scanning electron microscopy of Compritol(®) pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol(®) and Compritol(®) pellets, explained by Korsmeyer-Peppas (R(2) = 0.978-0.993) indicated

  1. Comparative steady-state pharmacokinetic study of an extended-release formulation of itopride and its immediate-release reference formulation in healthy volunteers

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    Yoon S

    2014-01-01

    Full Text Available Seonghae Yoon,1,* Howard Lee,2,* Tae-Eun Kim,1 SeungHwan Lee,1 Dong-Hyun Chee,3 Joo-Youn Cho,1 Kyung-Sang Yu,1 In-Jin Jang1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Clinical Trials Center, Seoul National University Hospital, 3AbbVie Ltd., Seoul, Republic of Korea *These authors contributed equally to this work Background: This study was conducted to compare the oral bioavailability of an itopride extended-release (ER formulation with that of the reference immediate-release (IR formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. Methods: A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22–48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax and area under the plasma concentration versus time curve over 24 hours after dosing (AUC0–24h, were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. Results: A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC0–24h were contained within the conventional bioequivalence range of 0.80–1.25 (0.94 [0.88–1.01], although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC0–24h was not affected. There were no serious adverse events and both formulations were

  2. A double-blind placebo-controlled study of fluvoxamine and imipramine in out-patients with primary depression.

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    Itil, T M; Shrivastava, R K; Mukherjee, S; Coleman, B S; Michael, S T

    1983-01-01

    1 A double-blind placebo-controlled study of fluvoxamine and imipramine was performed in a group of depressed patients. Twenty-two patients received fluvoxamine (mean dose 101 mg/day), 25 received imipramine (mean dose 127 mg/day) and 22 received placebo. 2 Apart from an increase in the SGOT and SGPT values of four imipramine patients, no statistically significant changes in haematology or urinalysis were judged to be medically relevant. Fluvoxamine exhibited fewer anticholinergic side effects than imipramine. 3 Both fluvoxamine treated patients and imipramine-treated patients exhibited a statistically significant improvement at the end of the 28-day treatment period with respect to the placebo patients, as measured using the Hamilton Rating Scale for Depression, and the Clinical Global Impression Scale. Evaluations of the results of the Beck Depression Inventory and the Profile of Mood States revealed a statistically significant improvement for imipramine patients with respect to placebo at week 4, but not for fluvoxamine patients. It is postulated on the basis of quantitative pharmaco-EEG findings, that the slight superiority of imipramine over fluvoxamine was due to underdosing of the latter.

  3. Fluvoxamine for fatigue in primary biliary cirrhosis and primary sclerosing cholangitis: a randomised controlled trial [ISRCTN88246634

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    Hansen Bettina E

    2004-07-01

    Full Text Available Abstract Background Fatigue is a major clinical problem in many patients with primary biliary cirrhosis (PBC and primary sclerosing cholangitis (PSC. An effective treatment has not been defined. Recently, a large proportion of patients with these diseases was found to have symptoms of depression. Because fatigue is a frequent symptom of depression and there is some evidence that treatment with an antidepressant improves fatigue in patients with fibromyalgia, we hypothesised that the antidepressant fluvoxamine might improve fatigue related to PBC and PSC. Methods Fatigued patients were randomised to receive fluvoxamine (75 mg BID or placebo for a six-week period. Fatigue and quality of life were quantified using a visual analogue scale, the Fisk Fatigue Severity Scale, the Multidimensional Fatigue Inventory and the SF-36. Results Seventeen and 16 patients were allocated to fluvoxamine and placebo, respectively. There was no statistically significant beneficial effect of fluvoxamine on fatigue or quality of life. The median VAS scores in the fluvoxamine and placebo groups were 7.40 and 7.45 at day 0, 6.9 and 7.15 at day 14, 7.45 and 7.65 at day 42 and 7.8 and 8.0 four weeks after treatment discontinuation. Conclusion We found no evidence for a beneficial effect of fluvoxamine on fatigue in these patients with cholestatic liver disease and severe chronic fatigue.

  4. Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis

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    Satoshi Takahashi

    2014-04-01

    Full Text Available To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011–2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33. The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43 and 37.2% (16/43, respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50. The microbiological eradication rates for the pathogens were 90.9% (30/33 for Neisseria gonorrhoeae, 91.5% (43/47 for Chlamydia trachomatis, 71.4% (5/7 for Mycoplasma genitalium, and 100% (13/13 for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120. The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.

  5. Critical appraisal of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia

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    Ayman A Hussein

    2010-04-01

    Full Text Available Ayman A Hussein, Stephen J NichollsCardiovascular Medicine Department, Cleveland Clinic Foundation, Cleveland, OH, USAAbstract: Niacin is a B-complex vitamin which has been used for decades for the management of mixed dyslipidemias and primary hypercholesterolemia. It decreases the risk of cardiovascular events either when used as a monotherapy or in combination with other lipid lowering medications. However, a major limitation to its use is niacin-induced flushing occurring even with the extended-release formulations. Laropiprant, a selective prostaglandin-2 receptor inhibitor, specifically targets the cascade of events causing the flushing. It has been recently used in combination with extended-release niacin. This article will review the early experience with this combination with focus on efficacy, safety, tolerability and current place in therapy. Early data are promising and suggest that more patients in clinical practice will benefit from niacin combined with laropiprant. Ongoing clinical trials will provide a better insight on the long-term safety of the drug and its efficacy for reducing cardiovascular events.Keywords: niacin, laropiprant, dyslipidemias, hypercholesterolemia

  6. Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

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    Sachiko Fukui

    2017-03-01

    Full Text Available The purpose of this study was to develop an extended-release (ER matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate (HPMCAS and hydroxypropylcellulose (HPC were selected as ER polymers for the ER matrix tablet (HPMCAS/HPC ER matrix tablet. Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed. In a USP apparatus 3 (bio-relevant dissolution method, dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product (OxyContin. Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroPlus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.

  7. Double-blind, placebo-controlled evaluation of extended-release bupropion in elderly patients with major depressive disorder.

    Science.gov (United States)

    Hewett, K; Chrzanowski, W; Jokinen, R; Felgentreff, R; Shrivastava, R K; Gee, M D; Wightman, D S; O'Leary, M C; Millen, L S; Leon, M C; Briggs, M A; Krishen, A; Modell, J G

    2010-04-01

    Major depressive disorder in the elderly is associated with increased morbidity and reduced quality of life. This 10 week, placebo-controlled study investigated the efficacy and tolerability of extended-release bupropion (150-300 mg once daily) in depressed patients aged 65 years or older. The statistical assumptions necessary for the validity of the protocol-specified analysis of covariance were not met for the analysis of the primary outcome variable (Montgomery-Asberg Depression Rating Scale total score at Week 10, last observation carried forward). Alternative statistical methods used for the analysis of this variable demonstrated statistical significance. Statistically significant improvements were observed on the majority of secondary end points when compared with placebo, including the health outcome measures for motivation and energy, and life satisfaction and contentment. Adverse events were generally mild to moderate and similar between treatment groups. This study demonstrated that the extended-release bupropion is an effective, well-tolerated treatment for major depression in the elderly.

  8. Single- and multiple-dose pharmacokinetics of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155 compared with immediate-release hydrocodone bitartrate/ibuprofen and immediate-release tramadol HCl/acetaminophen

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2015-09-01

    Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young41Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, 2Mallinckrodt Pharmaceuticals, 3Research and Development, Mallinckrodt Pharmaceuticals, 4Department of Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USAObjective: To characterize the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (IR/ER HB/APAP, IR HB/ibuprofen, and IR tramadol HCl/APAP.Methods: In this single-center, open-label, randomized, four-period crossover study, healthy participants received four treatments under fasted conditions: 1 a single dose of two IR/ER HB/APAP 7.5/325 mg tablets (15/650 mg total dose on day 1, followed by two tablets every 12 hours (q12h beginning on day 3; 2 a single dose of IR HB/ibuprofen 15/400 mg (divided as one 7.5/200 mg tablet at hour 0 and 6, followed by one tablet every 6 hours (q6h beginning on day 3; 3 a single dose of IR tramadol HCl/APAP 75/650 mg (divided as one 37.5/325 mg tablet at hour 0 and 6, followed by one tablet q6h beginning on day 3; and 4 a single dose of three IR/ER HB/APAP 7.5/325 mg tablets (22.5/975 mg total dose on day 1, a three-tablet initial dose at 48 hours followed by two-tablet doses q12h beginning on day 3. Hydrocodone and APAP single-dose and steady-state PK were assessed. Adverse events were monitored.Results: The PK analysis was carried out on 29 of 48 enrolled participants who completed all treatment periods. Single-dose hydrocodone exposure was similar for IR/ER HB/APAP 22.5/975 mg and IR HB/ibuprofen 15/400 mg; time to maximum observed plasma concentration was shorter and half-life was longer for IR/ER HB/APAP (22.5/975 mg and 15/650 mg vs IR HB/ibuprofen. Single-dose APAP exposure was similar for IR/ER HB/APAP 15/650 mg and IR tramadol HCl/APAP 75/650 mg. Steady-state hydrocodone and APAP exposures

  9. THE VERY LARGE ARRAY 1.4 GHz SURVEY OF THE EXTENDED CHANDRA DEEP FIELD SOUTH: SECOND DATA RELEASE

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Neal A. [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States); Bonzini, Margherita; Mainieri, Vincenzo; Padovani, Paolo; Rosati, Piero [European Southern Observatory, Karl-Schwarzschild-Strasse 2, D-85748 Garching bei Muenchen (Germany); Fomalont, Edward B.; Kellermann, Kenneth I. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States); Tozzi, Paolo; Vattakunnel, Shaji, E-mail: nmiller@astro.umd.edu [INAF Osservatorio Astronomico di Trieste, via G.B. Tiepolo 11, I-34131 Trieste (Italy)

    2013-04-01

    Deep radio observations at 1.4 GHz for the Extended Chandra Deep Field South were performed in 2007 June through September and presented in a first data release. The survey was made using six separate pointings of the Very Large Array with over 40 hr of observation per pointing. In the current paper, we improve on the data reduction to produce a second data release (DR2) mosaic image. This DR2 image covers an area of about a third of a square degree, reaches a best rms sensitivity of 6 {mu}Jy, and has a typical sensitivity of 7.4 {mu}Jy per 2.''8 by 1.''6 beam. We also present a more comprehensive catalog, including sources down to peak flux densities of five or more times the local rms noise along with information on source sizes and relevant pointing data. We discuss in some detail the consideration of whether sources are resolved under the complication of a radio image created as a mosaic of separate pointings each suffering some degree of bandwidth smearing, and the accurate evaluation of the flux densities of such sources. Finally, the radio morphologies and optical/near-IR counterpart identifications are used to identify 17 likely multiple-component sources and arrive at a catalog of 883 radio sources, which is roughly double the number of sources contained in the first data release.

  10. Minimal clinically important difference in Parkinson's disease as assessed in pivotal trials of pramipexole extended release.

    Science.gov (United States)

    Hauser, Robert A; Gordon, Mark Forrest; Mizuno, Yoshikuni; Poewe, Werner; Barone, Paolo; Schapira, Anthony H; Rascol, Olivier; Debieuvre, Catherine; Fräßdorf, Mandy

    2014-01-01

    Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson's Disease Rating Scale (UPDRS) scores in early Parkinson's disease (EPD) and for UPDRS scores and "OFF" time in advanced Parkinson's disease (APD). Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of pramipexole ER that included pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves "a little better" on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (pramipexole ER, pramipexole IR) for UPDRS II were -1.8 and -2.0, for UPDRS III -6.2 and -6.1, and for UPDRS II + III -8.0 and -8.1. MCIDs in APD for UPDRS II were -1.8 and -2.3, for UPDRS III -5.2 and -6.5, and for UPDRS II + III -7.1 and -8.8. MCID for "OFF" time (pramipexole ER, pramipexole IR) was -1.0 and -1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials.

  11. Role of extended release quetiapine in the management of bipolar disorders

    Directory of Open Access Journals (Sweden)

    Rayan K Al Jurdi

    2010-02-01

    Full Text Available Rayan K Al Jurdi1,2, Lena A Dixit1, Martha Sajatovic3 1Baylor College of Medicine, Department of Psychiatry, Houston, Texas, USA; 2South Central Mental Illness Research and Clinical Core, Department of Veterans Affairs, Houston, Texas; 3Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USAAbstract: Atypical antipsychotics have become a widely utilized component of the bipolar disorder treatment armamentarium, with approximately 45% of bipolar patients prescribed atypicals. Over the last decade all atypical drugs except for clozapine have received a Food and Drug Administration (FDA bipolar indication. In October 2008, the FDA approved quetiapine XR monotherapy for the treatment of acute depressive episodes of bipolar disorder and acute manic or mixed episodes in bipolar I disorder based on two placebo-control trials. Quetiapine was also approved as adjunct therapy with lithium and divalproex for the treatment of acute manic or mixed episodes as well as maintenance of bipolar I disorder. In contrast to immediate release quetiapine which may require a twice-daily regimen, the XR formulation is intended for once-daily administration. This drug profile of quetiapine XR will address chemistry, pharmacodynamics, pharmacokinetics, metabolism, safety and tolerability and clinical trials in bipolar disorder.Keywords: quetiapine XR, bipolar disorder

  12. Cost-effectiveness of extended-release methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder sub-optimally treated with immediate release methylphenidate.

    Directory of Open Access Journals (Sweden)

    Jurjen van der Schans

    Full Text Available Attention-Deficit/Hyperactivity Disorder (ADHD is a common psychiatric disorder in children and adolescents. Immediate-release methylphenidate (IR-MPH is the medical treatment of first choice. The necessity to use several IR-MPH tablets per day and associated potential social stigma at school often leads to reduced compliance, sub-optimal treatment, and therefore economic loss. Replacement of IR-MPH with a single-dose extended release (ER-MPH formulation may improve drug response and economic efficiency.To evaluate the cost-effectiveness from a societal perspective of a switch from IR-MPH to ER-MPH in patients who are sub-optimally treated.A daily Markov-cycle model covering a time-span of 10 years was developed including four different health states: (1 optimal response, (2 sub-optimal response, (3 discontinued treatment, and (4 natural remission. ER-MPH options included methylphenidate osmotic release oral system (MPH-OROS and Equasym XL/Medikinet CR. Both direct costs and indirect costs were included in the analysis, and effects were expressed as quality-adjusted life years (QALYs. Univariate, multivariate as well as probabilistic sensitivity analysis were conducted and the main outcomes were incremental cost-effectiveness ratios.Switching sub-optimally treated patients from IR-MPH to MPH-OROS or Equasym XL/Medikinet CR led to per-patient cost-savings of €4200 and €5400, respectively, over a 10-year treatment span. Sensitivity analysis with plausible variations of input parameters resulted in cost-savings in the vast majority of estimations.This study lends economic support to switching patients with ADHD with suboptimal response to short-acting IR-MPH to long-acting ER-MPH regimens.

  13. Effects of fluvoxamine on levels of dopamine, serotonin, and their metabolites in the hippocampus elicited by isolation housing and novelty stress in adult rats.

    Science.gov (United States)

    Miura, H; Qiao, H; Kitagami, T; Ohta, T; Ozaki, N

    2005-03-01

    The authors investigated the effects of fluvoxamine on neurochemical changes in the hippocampus elicited by isolation housing and novelty stress. Male F344 rats (11 w) were housed one per cage for four weeks. On each day of the last week (7 days) they were s.c. injected with fluvoxamine (20 mg/kg), and then subjected to novelty stress. Isolation housing significantly increased dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) levels, whereas fluvoxamine significantly decreased them. Isolation housing significantly increased the DOPAC/DA ratio. Fluvoxamine significantly decreased the DA level, and partially restored the DOPAC and 5-HIAA levels increased by isolation housing.

  14. Developments in managing severe chronic pain: role of oxycodone–naloxone extended release

    Directory of Open Access Journals (Sweden)

    Fanelli G

    2015-07-01

    Full Text Available Guido Fanelli,1 Andrea Fanelli2 1Anesthesia and Intensive Care Unit, University of Parma, Parma, 2Anesthesia and Intensive Care Unit, Policlinico S Orsola-Malpighi, Bologna, Italy Abstract: Chronic pain is a highly disabling condition, which can significantly reduce patients’ quality of life. Prevalence of moderate and severe chronic pain is high in the general population, and it increases significantly in patients with advanced cancer and older than 65 years. Guidelines for the management of chronic pain recommend opioids for the treatment of moderate-to-severe pain in patients whose pain is not responsive to initial therapies with paracetamol and/or nonsteroidal anti-inflammatory drugs. Despite their analgesic efficacy being well recognized, adverse events can affect daily functioning and patient quality of life. Opioid-induced constipation (OIC occurs in 40% of opioid-treated patients. Laxatives are the most common drugs used to prevent and treat OIC. Laxatives do not address the underlying mechanisms of OIC; for this reason, they are not really effective in OIC treatment. Naloxone is an opioid receptor antagonist with low systemic bioavailability. When administered orally, naloxone antagonizes the opioid receptors in the gut wall, while its extensive first-pass hepatic metabolism ensures the lack of antagonist influence on the central-mediated analgesic effect of the opioids. A prolonged-release formulation consisting of oxycodone and naloxone in a 2:1 ratio was developed trying to reduce the incidence of OIC maintaining the analgesic effect compared with use of the sole oxycodone. This review includes evidence related to use of oxycodone and naloxone in the long-term management of chronic non-cancer pain and OIC. Keywords: chronic pain, opioid-induced constipation, opioids, oxycodone–naloxone

  15. Validation of the IntelliCap® system as a tool to evaluate extended release profiles in human GI tract using metoprolol as model drug.

    Science.gov (United States)

    Söderlind, Erik; Abrahamsson, Bertil; Erlandsson, Fredrik; Wanke, Christoph; Iordanov, Ventzeslav; von Corswant, Christian

    2015-11-10

    A clinical study was conducted to validate the in vivo drug release performance of IntelliCap® CR capsules. 12 healthy, male volunteers were administered IntelliCap® CR capsules, filled with metoprolol as a BCS 1 model drug, and programmed to release the drug with 3 different release profiles (2 linear profiles extending over 6h and 14h, respectively, and a pulsed profile with two equal pulses separated by 5h) using a cross-over design. An oral metoprolol solution was included as a reference. Standard bioavailability variables were determined. In vivo drug release-time profiles for the IntelliCap® CR capsules were calculated from the plasma drug concentrations by deconvolution, and they were subsequently compared with the in vitro drug release profiles including assessment of level A in vitro/in vivo correlation (IVIVC). The relative bioavailability for the linear, extended release profiles was about 85% which is similar to other extended release administrations of metoprolol. There was an excellent agreement between the predetermined release profiles and the in vivo release for these two administrations. For IntelliCap® CR capsules programmed to deliver 2 distinct and equal drug pulses, the first pulse was delivered as expected whereas only about half of the second dose was released. Thus, it is concluded that the IntelliCap® system is well suited for the fast and reliable generation of in vivo pharmacokinetic data for extended release drug profiles, e.g. in context of regional drug absorption investigations. For immediate release pulses delivered in the distal GI tract this version of the device appears however less suitable.

  16. Sigma-1 receptor agonist fluvoxamine for delirium in intensive care units: report of five cases

    Directory of Open Access Journals (Sweden)

    Hashimoto Kenji

    2010-04-01

    Full Text Available Abstract Background Delirium is a highly prevalent disorder among older patients in intensive care units (ICUs. Although antipsychotic drugs are the medications most frequently used to treat this syndrome, these drugs are associated with a variety of adverse events, including sedation, extrapyramidal side effects, and cardiac arrhythmias. Drug treatment for delirium requires careful consideration of the balance between the effective management of symptoms and potential adverse effects. Methods We report on five Japanese men (an 84 year old (acute aortic dissociation: Stanford type A, a 55 year old (traumatic subarachnoid hemorrhage and brain contusion, a 76 year old (sepsis by pyelonephritis, an 85 year old (cerebral infarction, and an 86 year old (pulmonary emphysema and severe pneumonia in which the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the delirium of the patients. Results Delirium Rating Scale (DRS scores in these five patients dramatically decreased after treatment with fluvoxamine. Conclusion Doctors should consider fluvoxamine as an alternative approach to treating delirium in ICU patients in order to avoid the risk of side effects and increased mortality from antipsychotic drugs.

  17. Fluvoxamine alters the activity of energy metabolism enzymes in the brain

    Directory of Open Access Journals (Sweden)

    Gabriela K. Ferreira

    2014-09-01

    Full Text Available Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent.

  18. Report of two cases where sleep related eating behavior occurred with the extended-release formulation but not the immediate-release formulation of a sedative-hypnotic agent.

    Science.gov (United States)

    Chiang, Ambrose; Krystal, Andrew

    2008-04-15

    We report two cases in which amnestic sleep related eating disorder (SRED) occurred with extended-release zolpidem but not with the immediate-release formulation. These cases illustrate how even relatively small differences such as formulation can affect the likelihood of experiencing such events.

  19. Safety and efficacy of clonidine and clonidine extended-release in the treatment of children and adolescents with attention deficit and hyperactivity disorders

    Directory of Open Access Journals (Sweden)

    Ming X

    2011-09-01

    Full Text Available Xue Ming1, Martha Mulvey1, Sharanya Mohanty2, Viraj Patel21Department of Neurosciences, University of Medicine and Dentistry New Jersey, New Jersey Medical School, Newark, 2The College of New Jersey, Ewing, NJ, USAAbstract: Clonidine has been used offlabel in children and adolescents with attention deficit and hyperactivity disorders (ADHD with or without comorbidities. Clonidine extended-release was recently approved by the US Food and Drug Administration for ADHD in children. This review evaluates the efficacy and safety of clonidine extended-release and clonidine in children and adolescents with ADHD. A search of the Medline database and clinical trials register from 1996–2011 yielded ten clinical trials for critical evaluation of efficacy and safety. Eight of the ten trials reviewed were double-blinded and placebo-controlled. Nine of the ten trials utilized multiple outcome measures. Both clonidine extended-release and clonidine, as monotherapy or adjunctive therapy, were reported to be efficacious in treating ADHD symptoms in children and adolescents with or without comorbid disorders in nine of the ten clinical trials. One study showed clonidine to be ineffective in improving performance of a single task, at a specific point in time, in a small number of subjects. All of the studies that evaluated safety reported clonidine and clonidine extended-release to be well tolerated. The side effects of clonidine included somnolence, fatigue, headache, bradycardia, hypotension, and clinically insignificant electrocardiographic changes. However, there are historical anecdotal reports of serious cardiac side effects, including death in cases with other risk factors. None of the studies compared clonidine extended-release with clonidine in subjects with ADHD. Therefore, it is not clear whether clonidine extended-release is advantageous over clonidine, with regard to either efficacy or safety. It is equally unclear whether clonidine or clonidine

  20. Switch from Immediate-release Pramipexole to Extended-release Pramipexole: The Safety and Efficacy Characteristics of Sixty-eight Patients

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    Müge Kuzu

    2016-09-01

    Full Text Available Objective: To evaluate the safety and efficacy of switching from immediate-release pramipexole (pex to extended-release pramipexole (pex-ER. Materials and Methods: Pex-ER became available in Turkey about a year ago, since then we documented satisfactory information on patients (26 women; 38% who were switched from pex to pex-ER. We recorded pre- and post-switch pex and levodopa, equivalent doses of other anti-parkinsonian medication, and analyzed the frequency and nature of reported adverse effects. Results: The mean age of the patients was 63.3 years (range, 44-88 years, and the mean disease duration was 7.1 years (range, 1-27 years. The other drugs were levodopa (57 patients, 82.6%, entacapone (24 patients, 34.58%, rasagiline (20 patients, 29%, amantadine (18 patients, 26.1%, and apomorphine (six patients, 8.7%. Switch from pex to pex-ER was uneventful in 62 (91.2% patients. Adverse events were reported in six (8.8% patients: ankle swelling (two patients, nausea (one patient, dyskinesia (one patient, hypersexuality (one patient, and psychosis (one patient. Problems resolved with further medication change in two patients. Four patients preferred to return to pex. Conclusion: The great majority of patients (91.2% switched from three times daily pex to once daily pex-ER uneventfully. A slight increase in pex daily dose, which was tailored according to patients’ symptomatic needs, resulted in an increase in post-switch levodopa equivalent doses. Our experience is compatible with previously reported studies.

  1. The ATLAS 5.5 GHz Survey of the Extended Chandra Deep Field South: The Second Data Release

    CERN Document Server

    Huynh, M T; Hopkins, A M; Norris, R P; Seymour, N

    2015-01-01

    We present a new image of the 5.5 GHz radio emission from the extended Chandra Deep Field South. Deep radio observations at 5.5 GHz were obtained in 2010 and presented in the first data release. A further 76 hours of integration has since been obtained, nearly doubling the integration time. This paper presents a new analysis of all the data. The new image reaches 8.6 microJy rms, an improvement of about 40% in sensitivity. We present a new catalogue of 5.5 GHz sources, identifying 212 source components, roughly 50% more than were detected in the first data release. Source counts derived from this sample are consistent with those reported in the literature for S_{5.5GHz} > 0.1 mJy but significantly lower than published values in the lowest flux density bins (S_{5.5GHz} 0.5 mJy, consistent with the flattening of the spectral index observed in 5 GHz sub-mJy samples. The median spectral index of the whole sample is \\alpha_{med} = -0.58, indicating that these observations may be starting to probe the star forming...

  2. The VLA 1.4GHz Survey of the Extended Chandra Deep Field South: Second Data Release

    CERN Document Server

    Miller, N A; Fomalont, E B; Kellermann, K I; Mainieri, V; Padovani, P; Rosati, P; Tozzi, P; Vattakunnel, S

    2013-01-01

    Deep radio observations at 1.4GHz for the Extended Chandra Deep Field South were performed in June through September of 2007 and presented in a first data release (Miller et al. 2008). The survey was made using six separate pointings of the Very Large Array (VLA) with over 40 hours of observation per pointing. In the current paper, we improve on the data reduction to produce a second data release (DR2) mosaic image. This DR2 image covers an area of about a third of a square degree and reaches a best rms sensitivity of 6 uJy and has a typical sensitivity of 7.4 uJy per 2.8" by 1.6" beam. We also present a more comprehensive catalog, including sources down to peak flux densities of five or more times the local rms noise along with information on source sizes and relevant pointing data. We discuss in some detail the consideration of whether sources are resolved under the complication of a radio image created as a mosaic of separate pointings each suffering some degree of bandwidth smearing, and the accurate eval...

  3. Methylphenidate Efficacy: Immediate versus Extended Release at Short Term in Mexican Children with ADHD Assessed by Conners Scale and EEG

    Science.gov (United States)

    Alatorre-Miguel, Efren; Zambrano-Sánchez, Elizabeth; Reyes-Legorreta, Celia

    2015-01-01

    Attention deficit hyperactivity disorder (ADHD) affects 5-6% of school aged children worldwide. Pharmacological therapy is considered the first-line treatment and methylphenidate (MPH) is considered the first-choice medication. There are two formulations: immediate release (IR) MPH and long-acting (or extended release) formulation (MPH-ER). In this work, we measure the efficacy of treatment for both presentations in one month with Conners' scales and electroencephalography (EEG). Results. for IR group, in parents and teachers Conners test, all items showed significant differences, towards improvement, except for teachers in perfectionism and emotional instability. For ER group in parent's Conners test, the items in which there were no significant differences are psychosomatic and emotional instability. For teachers, there were no significant differences in: hyperactivity and perfectionism. Comparing the Conners questionnaires (parents versus teachers) we find significant differences before and after treatment in hyperactivity, perfectionism, psychosomatics, DSM-IV hyperactive-impulsive, and DSM-IV total. In the EEG the Wilcoxon test showed a significant difference (P < 0.0001). As we can see, both presentations are suitable for managing the ADHD and have the same effect on the symptomatology and in the EEG. PMID:25838946

  4. Methylphenidate Efficacy: Immediate versus Extended Release at Short Term in Mexican Children with ADHD Assessed by Conners Scale and EEG

    Directory of Open Access Journals (Sweden)

    Alfredo Durand-Rivera

    2015-01-01

    Full Text Available Attention deficit hyperactivity disorder (ADHD affects 5-6% of school aged children worldwide. Pharmacological therapy is considered the first-line treatment and methylphenidate (MPH is considered the first-choice medication. There are two formulations: immediate release (IR MPH and long-acting (or extended release formulation (MPH-ER. In this work, we measure the efficacy of treatment for both presentations in one month with Conners’ scales and electroencephalography (EEG. Results. for IR group, in parents and teachers Conners test, all items showed significant differences, towards improvement, except for teachers in perfectionism and emotional instability. For ER group in parent’s Conners test, the items in which there were no significant differences are psychosomatic and emotional instability. For teachers, there were no significant differences in: hyperactivity and perfectionism. Comparing the Conners questionnaires (parents versus teachers we find significant differences before and after treatment in hyperactivity, perfectionism, psychosomatics, DSM-IV hyperactive-impulsive, and DSM-IV total. In the EEG the Wilcoxon test showed a significant difference (P<0.0001. As we can see, both presentations are suitable for managing the ADHD and have the same effect on the symptomatology and in the EEG.

  5. Evaluation of a single-dose, extended-release epidural morphine formulation for pain control after lumbar spine surgery.

    Science.gov (United States)

    Vineyard, Joseph C; Toohey, John S; Neidre, Arvo; Fogel, Guy; Joyner, Robert

    2014-01-01

    DepoDur, an extended-release epidural morphine, has been used effectively for postoperative pain control following many orthopaedic and general surgery procedures and has provided prolonged analgesia when compared with Duramorph. The goal of this article was to compare the safety and analgesic efficacy of DepoDur versus Duramorph after lumbar spine surgery. A prospective, randomized, double-blind clinical study was completed at a single extended-stay ambulatory surgery center. All patients over 18 undergoing posterior lumbar spine fusions were considered for the study. Sixty patients were randomly assigned to a control or treatment group. The control group received DepoDur before surgery, while the treatment group received Duramorph. Although results show no significant differences between the two groups in postoperative visual analog pain scale scores, use of pain medication, and adverse events, subjects receiving DepoDur were less likely to receive Naloxone and oxygen supplementation, experience nausea or fever, and were more likely to experience hypotension. DepoDur proved to be safe and effective, offering similar prolonged analgesic activity when compared with Duramorph.

  6. Psychosocial outcomes in patients with recurrent major depressive disorder during 2 years of maintenance treatment with venlafaxine extended release

    Science.gov (United States)

    Trivedi, Madhukar H.; Dunner, David L.; Kornstein, Susan G.; Thase, Michael E.; Zajecka, John M.; Rothschild, Anthony J.; Friedman, Edward S.; Shelton, Richard C.; Keller, Martin B.; Kocsis, James H.; Gelenberg, Alan

    2013-01-01

    Background Psychosocial outcomes from the Prevention of Recurrent Episodes of Depression with Venlafaxine ER for Two Years (PREVENT) study were evaluated. Methods Adult outpatients with recurrent major depressive disorder (MDD) and response or remission following 6-month continuation treatment with venlafaxine extended release (ER) were randomized to receive venlafaxine ER or placebo for 1 year. Patients without recurrence on venlafaxine ER during year 1 were randomized to venlafaxine ER or placebo for year 2. Psychosocial functioning was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire—Short Form (Q-LES-Q), Life EnjoymentScale—Short Version (LES-S), Social Adjustment Scale—Self-Report (SAS-SR) total and individual factors, Short Form Health Survey (SF-36) (vitality, social functioning, and role function-emotional items), and Longitudinal Interval Follow-up Evaluation (LIFE). Results At year 1 end, better overall psychosocial functioning was seen among patients randomly assigned to venlafaxine ER (n=129) vs placebo (n=129), with significant differences at end point on SF-36 role function-emotional, Q-LES-Q, and SAS-SR total, and work, house work, social/leisure, and extended-family factor scores (p≤0.05). At year 2 end, significant differences favored venlafaxine ER (n=43) vs placebo (n=40)on SF-36 vitality and rolefunction-emotional, Q-LES-Q, LES-S, LIFE, and SAS-SR total, social/leisure, and extended-family factor scores (p≤0.05). Limitations Patients with chronic MDD or treatment resistance were excluded and long-term specialist care was a financial incentive for treatment compliance. Discontinuation-related adverse events may have compromised the integrity of the treatment blind. Conclusions For patients with recurrent MDD, 2 years’ maintenance therapy with venlafaxine ER may improve psychosocial functioning vs placebo. PMID:20510459

  7. Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression.

    Science.gov (United States)

    Ofori-Kwakye, Kwabena; Mfoafo, Kwadwo Amanor; Kipo, Samuel Lugrie; Kuntworbe, Noble; Boakye-Gyasi, Mariam El

    2016-01-01

    The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (∼24 h) and metformin (∼8-12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct

  8. Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant.

    Science.gov (United States)

    Ali, Moazzam; Akin, Ayse; Bahamondes, Luis; Brache, Vivian; Habib, Ndema; Landoulsi, Sihem; Hubacher, David

    2016-11-01

    Is it possible to extend the use of the 3-year one-rod etonogestrel (ENG)-releasing subdermal contraceptive implant to 5 years? The extended use of the one-rod ENG-releasing subdermal contraceptive implant showed 100% efficacy in years 4 and 5. The initial regulated trials on the ENG-releasing subdermal contraceptive implant conducted in the 1990 s were designed to measure cumulative 3-year efficacy. The ENG-implant has both well established safety and efficacy for up to 3 years. Pharmacokinetic data on ENG show high levels at 3 years and some previous clinical research confirms efficacy beyond the current approved duration of 3 years. Today, many women, because the labeled duration has been reached, have the ENG implant removed at 3 years, increasing costs, inconvenience and risks. For the first 3 years, this study was an open-label, multi-centre randomized trial comparing the 3-year ENG implant to the 5-year levonorgestrel (LNG)-releasing implant. After 3 years, a subset of 390 ENG participants, consented to extended use. We compared efficacy, side effects and removal procedures of both implants. We used Kaplan-Meier (K-M) analysis. We included an observational cohort of copper intrauterine device (IUD) users as non-users of hormonal contraceptive method for comparative purposes. The study took place in family planning clinics in seven countries worldwide. Women were enlisted after an eligibility check and informed consent, and 1328 women were enrolled: 390, 522 and 416 in the ENG-implant, LNG-implant and IUD groups, respectively. Over 200 women used the ENG implant for at least 5 years. No pregnancies occurred during the additional 2 years of follow up in the ENG or LNG implant group. The overall 5-year K-M cumulative pregnancy rates for ENG- and LNG- implants were 0.6 per 100 women-years (W-Y) [95% confidence interval (CI): 0.2-1.8] and 0.8 per 100 W-Y [95% CI: 0.2-2.3], respectively. Complaints of bleeding changes were similar; however, ENG-users were more

  9. Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant

    Science.gov (United States)

    Ali, Moazzam; Akin, Ayse; Bahamondes, Luis; Brache, Vivian; Habib, Ndema; Landoulsi, Sihem; Hubacher, David

    2016-01-01

    STUDY QUESTION Is it possible to extend the use of the 3-year one-rod etonogestrel (ENG)-releasing subdermal contraceptive implant to 5 years? SUMMARY ANSWER The extended use of the one-rod ENG-releasing subdermal contraceptive implant showed 100% efficacy in years 4 and 5. WHAT IS KNOWN ALREADY The initial regulated trials on the ENG-releasing subdermal contraceptive implant conducted in the 1990 s were designed to measure cumulative 3-year efficacy. The ENG-implant has both well established safety and efficacy for up to 3 years. Pharmacokinetic data on ENG show high levels at 3 years and some previous clinical research confirms efficacy beyond the current approved duration of 3 years. Today, many women, because the labeled duration has been reached, have the ENG implant removed at 3 years, increasing costs, inconvenience and risks. STUDY DESIGN SIZE, DURATION For the first 3 years, this study was an open-label, multi-centre randomized trial comparing the 3-year ENG implant to the 5-year levonorgestrel (LNG)-releasing implant. After 3 years, a subset of 390 ENG participants, consented to extended use. We compared efficacy, side effects and removal procedures of both implants. We used Kaplan–Meier (K–M) analysis. We included an observational cohort of copper intrauterine device (IUD) users as non-users of hormonal contraceptive method for comparative purposes. PARTICIPANTS/MATERIALS, SETTING, METHODS The study took place in family planning clinics in seven countries worldwide. Women were enlisted after an eligibility check and informed consent, and 1328 women were enrolled: 390, 522 and 416 in the ENG-implant, LNG-implant and IUD groups, respectively. MAIN RESULTS AND THE ROLE OF CHANCE Over 200 women used the ENG implant for at least 5 years. No pregnancies occurred during the additional 2 years of follow up in the ENG or LNG implant group. The overall 5-year K–M cumulative pregnancy rates for ENG- and LNG- implants were 0.6 per 100 women-years (W-Y) [95

  10. Comparative efficacy and safety of extended-release and instant-release tolterodine in children with neural tube defects having cystometric abnormalities.

    Science.gov (United States)

    Mahanta, Kinkar; Medhi, Bikas; Kaur, Balpinder; Narasimhan, Kannan Laksmi

    2008-04-01

    To evaluate the comparative efficacy and safety of extended-release (ER) and instant-release (IR) tolterodine preparations in a pediatric population with neural tube defects having cystometric abnormalities. Twenty-five patients with neural tube defects and a similar demographic profile underwent a routine hemogram, liver function tests, renal function tests, urine culture, X-ray lumbo-sacral spine, and renal and bladder ultrasound. Vesicoureteric reflux was diagnosed by micturating cystourethrogram under fluoroscopy. Dimercaptosuccinic acid renal scintigraphy was performed to study the presence or absence of renal scars. Patients were treated with tolterodine ER (Group I: 2mg once daily for 21 days) and tolterodine IR (Group II: 2mg twice daily for 21 day) in a cross-over study with a 10-day washout period between administrations. Evaluation was by subjective assessment, visual analog scale, urodynamic assessment and adverse drug reaction monitoring. There was ultrasound evidence of hydroureteronephrosis in 20% of the patients. One patient out of 25 had impaired renal function and eight patients had renal scarring on dimercaptosuccinic acid scans. Both forms of the drug increased the maximum cystometric bladder capacity, decreased detrusor leak pressures and increased compliance compared to pre-therapy levels (P=0.0001). Visual analog scale showed a significant clinical improvement with both ER and IR tolterodine. A significant increase in maximum bladder capacity in the group receiving IR tolterodine as compared to the ER preparation was noted (P=0.0001). The decrease in detrusor leak pressures and improvement in compliance were not significantly different between the groups. No adverse effects of hyperpyrexia, flushing or intolerance to outdoor temperatures, or dryness of mouth were observed in either group. No patient suffered from constipation. ER tolterodine 2mg once daily is as effective and well tolerated in children with neurogenic bladder as IR

  11. Enabling clinical development of an HIV attachment inhibitor through innovative pharmaceutical development: novel extended-release delivery of prodrug

    Directory of Open Access Journals (Sweden)

    M Tobyn

    2012-11-01

    Full Text Available Background: HIV-1 attachment inhibitors are a new class of viral entry inhibitors which target viral gp120 preventing attachment of virus to its host cell receptor CD4. This class presents major challenges for development based upon low solubility and short half-lives. For progression into clinical studies, requirements include reliable and reproducible absorption from a tolerable and convenient oral dosing regimen. Methods: A series of highly soluble prodrugs were designed to overcome the poor absorption caused by the low solubility of the active compounds. A regional absorption study was conducted to assess the uptake of active throughout the gastro-intestinal tract following oral prodrug delivery. An extended-release (ER strategy was subsequently devised to optimise tolerability, decrease peak to trough ratios and reduce frequency of dosing. In silico absorption modelling was used to verify feasibility and drive in vitro testing leading to dosage form development and selection. The performance of the ER dosage form was verified in vivo prior to use in clinical studies. Results: Phosphonooxymethyl prodrugs with aqueous solubilities in excess of 250 mg/mL were synthesised and shown to be readily converted to parent compound via alkaline phosphatase in vitro. Results of regional absorption studies for the selected compound, BMS-663068, confirmed the rapid absorption but short half-life of active following oral administration of prodrug. Delivery to specific regions throughout the GI tract showed absorption of active to be subject to regional variation with an extent of colonic absorption of approximately 40% of intestinal absorption. Incorporation of this data into an in silico model guided development of an ER tablet which releases prodrug over 24 hours and achieves the required exposure, pharmacokinetics and reproducibility in vivo. Conclusions: The novel approach of combining prodrug synthesis and ER formulation has enabled clinical

  12. Efficacy, safety, and tolerability of overnight switching from immediate- to once daily extended-release pramipexole in early Parkinson's disease.

    Science.gov (United States)

    Rascol, Olivier; Barone, Paolo; Hauser, Robert A; Mizuno, Yoshikuni; Poewe, Werner; Schapira, Anthony H V; Salin, Laurence; Sohr, Mandy; Debieuvre, Catherine

    2010-10-30

    The aim of this article is to test the feasibility, in early Parkinson's disease (PD), of an overnight switch from immediate-release (IR) pramipexole to a new once-daily extended-release (ER) formulation. Nonfluctuating patients on pramipexole IR three-times daily, alone or with levodopa, for early PD were randomly switched overnight to double-blind IR three-times daily (N = 52) or ER once-daily (N = 104) at initially unchanged daily dosage. Successful switching (defined as no worsening >15% of baseline UPDRS II+III score and no drug-related adverse event withdrawal) was assessed at 9 weeks, after optional dosage adjustments (primary endpoint), and at 4 weeks, before adjustment. Other secondary endpoints included adjusted mean changes from baseline in UPDRS scores and proportion of responders based on Clinical or Patient Global Impression (CGI/PGI). Absolute difference between percentage of successful switch to ER versus IR was tested for ER noninferiority, defined as a 95% confidence-interval lower bound not exceeding -15%. At 9 weeks, 84.5% of the ER group had been successfully switched, versus 94.2% for IR. Noninferiority was not demonstrated, with a difference of -9.76% (95% CI: [-18.81%, +1.66%]). At 4 weeks, 81.6% of the ER group had been successfully switched, versus 92.3% for IR, a difference of -10.75% (95% CI: [-20.51%, +1.48%]). UPDRS changes and CGI/PGI analyses showed no differences between the groups. Both formulations were safe and well tolerated. Pramipexole ER was not equivalent to IR, but the difference was marginal. The fact that >80% of the patients successfully switched overnight at unchanged dosage shows that this practice was feasible in most patients.

  13. Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder.

    Science.gov (United States)

    Kreder, K; Mayne, C; Jonas, U

    2002-06-01

    The objective of the present study was to examine the long-term safety, tolerability and efficacy of tolterodine extended-release (ER) in patients who had completed 12 weeks' treatment in a randomised, double-blind study comparing tolterodine ER 4 mg once daily (qd), tolterodine immediate-release (IR) 2mg twice daily and placebo. Of the 1377 patients completing the 12-week study, a total of 1077 (78%) chose to continue with 12 months' open-label treatment with tolterodine ER 4 mg once daily, irrespective of their previous treatment. Safety was assessed after 3, 6, 9 and 12 months' treatment in the study. Efficacy was evaluated from micturition diary variables and patients' perception of bladder condition and urgency following 3 and 12 months' treatment. 71% of patients completed the 12-month study. Tolterodine ER was safe and well tolerated. Adverse events of the general (14.5%), autonomic (13.2%), gastrointestinal (11.4%), respiratory (9.8%) and urinary (9.1%) systems were the most frequently reported. Dry mouth was the most common event, occurring in 12.9% of patients, and was generally mild in severity. Other adverse events occurred in less than 5% of patients. There was no increase in the frequency of adverse events with long-term relative to short-term treatment. The efficacy of tolterodine was maintained over the 12-month treatment period; relative to baseline there were reductions in the number of incontinence episodes per week (median change -83%) and micturitions per 24 hours (median change -21%) and an increase in volume voided (median change +25%) after 12 months' treatment. An improvement in patient perception of their bladder condition was found in 75% of patients completing the study, and 51% had an improvement in patient perception of urgency. Tolterodine ER 4mg qd displayed a favourable safety, tolerability and efficacy profile during 12 months' treatment of patients with overactive bladder.

  14. Combination of niacin extended-release and simvastatin results in a less atherogenic lipid profile than atorvastatin monotherapy

    Directory of Open Access Journals (Sweden)

    William Insull Jr

    2010-11-01

    Full Text Available William Insull Jr1, Peter P Toth2, H Robert Superko3, Roopal B Thakkar4, Scott Krause4, Ping Jiang4, Rhea A Parreno4, Robert J Padley41Baylor College of Medicine and Methodist Hospital, Houston, Texas; 2University of Illinois College of Medicine, Peoria, Illinois; 3Celera, Alameda, California, Mercer University, Atlanta, Georgia; 4Abbott, Abbott Park, Illinois, USAObjective: To compare the effects of combination niacin extended-release + simvastatin (NER/S versus atorvastatin alone on apolipoproteins and lipid fractions in a post hoc analysis from SUPREME, a study which compared the lipid effects of niacin extended-release + simvastatin and atorvastatin in patients with hyperlipidemia or mixed dyslipidemia.Patients and methods: Patients (n = 137 with dyslipidemia (not previously receiving statin therapy or having discontinued any lipid-altering treatment 4–5 weeks prior to the study received NER/S (1000/40 mg/day for four weeks, then 2000/40 mg/day for eight weeks or atorvastatin 40 mg/day for 12 weeks. Median percent changes in apolipoprotein (apo A-1, apo B, and the apo B:A-I ratio, and nuclear magnetic resonance lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon rank-sum test and Fisher’s exact test.Results: NER/S treatment produced significantly greater percent changes in apo A-I and apo B:A-I, and, at the final visit, apo B <80 mg/dL was attained by 59% versus 33% of patients, compared with atorvastatin treatment (P = 0.003. NER/S treatment resulted in greater percent reductions in calculated particle numbers for low-density lipoprotein (LDL, 52% versus 43%; P = 0.022, small LDL (55% versus 45%; P = 0.011, very low-density lipoprotein (VLDL and total chylomicrons (63% versus 39%; P < 0.001, and greater increases in particle size for LDL (2.7% versus 1.0%; P = 0.007 and VLDL (9.3% versus 0.1%; P < 0.001, compared with atorvastatin.Conclusion: NER/S treatment significantly improved apo A-I levels and the apo

  15. Profile of guanfacine extended release and its potential in the treatment of attention-deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Martinez-Raga J

    2015-05-01

    Full Text Available Jose Martinez-Raga,1,2 Carlos Knecht,3 Raquel de Alvaro4 1Teaching Unit of Psychiatry and Psychological Medicine, University Hospital Doctor Peset, University of Valencia, 2CEU Cardenal Herrera University, 3Área de Salud Mental, Hospital Padre Jofré, Valencia, 4Hospital General, Consorcio Hospitalario Provincial, Castellon, Spain Abstract: The α2-adrenergic receptor agonist guanfacine, in its extended-release formulation (GXR, is the most recent nonstimulant medication approved in several countries for the treatment of attention-deficit hyperactivity disorder (ADHD as monotherapy and as adjunctive pharmacotherapy to stimulants in children and adolescents. The present paper aims to review comprehensively and critically the pharmacodynamic and pharmacokinetic characteristics and the published evidence on the efficacy and safety profile of GXR in the treatment of ADHD. A comprehensive search of relevant databases (PubMed, Embase, and PsycInfo was conducted to identify studies published in peer-reviewed journals until January 15, 2015. Though the precise mechanism of action of guanfacine in the treatment of ADHD is not fully understood, it is thought to act directly by enhancing noradrenaline functioning via α2A-adrenoceptors in the prefrontal cortex. Weight-adjusted doses should be used, with a dosing regime on a milligram per kilogram basis, starting at doses in the range 0.05–0.08 mg/kg/day, up to 0.12 mg/kg/day. As evidenced in short-term randomized controlled trials and in long-term open-label extension studies, GXR has been shown to be effective as monotherapy in the treatment of ADHD. Furthermore, GXR has also been found to be effective as adjunctive therapy to stimulant medications in patients with suboptimal responses to stimulants. Many of the adverse reactions associated with GXR, particularly sedation-related effects, were dose-related, transient, mild to moderate in severity, and did not interfere with attention or overall

  16. Population pharmacokinetics of methylphenidate hydrochloride extended-release multiple-layer beads in pediatric subjects with attention deficit hyperactivity disorder

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    Teuscher NS

    2015-05-01

    Full Text Available Nathan S Teuscher,1 Akwete Adjei,2 Robert L Findling,3,4 Laurence L Greenhill,5 Robert J Kupper,2 Sharon Wigal6 1PK/PD Associates, Trophy Club, TX, 2Rhodes Pharmaceuticals L.P., Coventry, RI, 3Department of Psychiatric Services and Research, Kennedy Krieger Institute, Baltimore, MD, 4Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, 5Department of Psychiatry, Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY, 6AVIDA Inc., Newport Beach, CA, USA Abstract: A new multilayer-bead formulation of extended-release methylphenidate hydrochloride (MPH-MLR has been evaluated in pharmacokinetic studies in healthy adults and in Phase III efficacy/safety studies in children and adolescents with attention deficit hyperactivity disorder (ADHD. Using available data in healthy adults, a two-input, one-compartment, first-order elimination population pharmacokinetic model was developed using nonlinear mixed-effect modeling. The model was then extended to pediatric subjects, and was found to adequately describe plasma concentration–time data for this population. A pharmacokinetic/pharmacodynamic model was also developed using change from baseline in the ADHD Rating Scale (ADHD-RS-IV total scores from a pediatric Phase III trial and simulated plasma concentration–time data. During simulations for each MPH-MLR dose level (10–80 mg, increased body weight resulted in decreased maximum concentration. Additionally, as maximum concentration increased, ADHD-RS-IV total score improved (decreased. Knowledge of the relationship between dose, body weight, and clinical response following the administration of MPH-MLR in children and adolescents may be useful for clinicians selecting initial dosing of MPH-MLR. Additional study is needed to confirm these results. Keywords: population pharmacokinetics, Aptensio XR™, MPH-MLR, methylphenidate

  17. Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression

    OpenAIRE

    Ofori-Kwakye, Kwabena; Mfoafo, Kwadwo Amanor; Kipo, Samuel Lugrie; Kuntworbe, Noble; Boakye-Gyasi, Mariam EL

    2015-01-01

    The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) ...

  18. Assessment of Alcohol-Induced Dose Dumping with a Hydrocodone Bitartrate Extended-Release Tablet Formulated with CIMA® Abuse Deterrence Technology

    OpenAIRE

    Darwish, Mona; Bond, Mary; Yang, Ronghua; Tracewell, William; Robertson, Philmore

    2015-01-01

    Background Greater drug content requirements for extended-release (ER) opioids necessitate greater protection against dose dumping. Hydrocodone ER employs the CIMA® Abuse-Deterrence Technology platform, which provides resistance against rapid release of the active moiety when the tablet is manipulated or taken with alcohol. Objective Assess effects of alcohol on hydrocodone ER pharmacokinetics. Study Design Open-label, crossover (January 25–April 30, 2010). Setting Single center. Participants...

  19. Effect of Extended-Release Niacin/Laropiprant Combination on Plasma Adiponectin and Insulin Resistance in Chinese Patients with Dyslipidaemia

    Directory of Open Access Journals (Sweden)

    Miao Hu

    2015-01-01

    Full Text Available Objectives. This study examined whether the increase of adiponectin associated with extended-release (ER niacin/laropiprant combination attenuates the adverse effect of niacin on glucose and insulin resistance in Hong Kong Chinese patients with dyslipidaemia. Methods. Patients (N=121 were treated with ER niacin/laropiprant 1 g/20 mg for 4 weeks and then the dose was doubled for an additional 8 weeks. Measurements of fasting lipids, glucose, insulin, and adiponectin were performed at baseline and during the study. Results. There were significant (P<0.001 increases in glucose (9.4 ± 13.1%, insulin (70.2 ± 91.0%, HOMA-IR (87.8 ± 103.9%, and adiponectin (169.3 ± 111.6%. The increase in adiponectin was significantly associated with increase in glucose (r=0.221, P<0.05, insulin (r=0.184, P<0.05, and HOMA-IR (r=0.237, P<0.01 and the association remained significant after adjustment for changes in body weight or body fat mass. Conclusion. Treatment with ER niacin/laropiprant led to a significant increase in adiponectin levels but worsening of glucose levels and insulin resistance, and the increase in adiponectin and insulin resistance were correlated suggesting the increase in adiponectin did not ameliorate the deterioration in insulin resistance. Clinical trial is registered with number on WHO-ICTRP: ChiCTR-ONC-10001038.

  20. Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial*

    Science.gov (United States)

    Lofwall, Michelle R.; Babalonis, Shanna; Nuzzo, Paul A.; Siegel, Anthony; Campbell, Charles; Walsh, Sharon L.

    2013-01-01

    Background Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: 1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and 2) whether cessation of ER tramadol produces opioid withdrawal. Methods Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. Results Use of breakthrough withdrawal medication differed significantly (ptramadol 200 mg produced significantly lower peak ratings than placebo on ratings of insomnia, lacrimation, muscular tension, and sneezing. Only tramadol 600 mg produced miosis in Phase 1. In Phase 2, tramadol 600 mg produced higher peak ratings of rhinorrhea, irritable, depressed, heavy/sluggish, and hot/cold flashes than placebo. There were no serious adverse events and no signal of abuse liability for tramadol. Conclusions ER tramadol 200 mg modestly attenuated opioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal. PMID:23755929

  1. Current and future development of extended-release, abuse-deterrent opioid formulations in the United States.

    Science.gov (United States)

    Webster, Lynn R; Markman, John; Cone, Edward J; Niebler, Gwendolyn

    2017-01-01

    Prescription opioid misuse and abuse in the United States (US) is epidemic and is a major burden on health-care resources and costs to society. The need to significantly reduce the risks of prescription opioid misuse and abuse must be balanced with the important needs of patients with chronic pain who may benefit from treatment with opioids. The use of abuse-deterrent formulations (ADFs) of prescription opioids is one approach that could reduce the risk of prescription opioid abuse and misuse while maintaining access to opioids. ADF opioids have properties that make their abuse more difficult, less attractive, or less rewarding. In 2015, the US Food and Drug Administration issued final guidance to industry for the development of ADF opioids that recommended specific studies be conducted to demonstrate the abuse-deterrent properties of new opioid formulations. The technologies and the preclinical and clinical development of ADF opioids are rapidly evolving. This review provides an overview of the required testing for product labeling that includes language about the abuse-deterrent features of an ADF opioid. The objective of this review is to inform and help health-care providers understand the unique development of extended-release ADF opioids and their place in the treatment of patients with pain.

  2. Analysis of potentially predictive factors of efficacy of adjunct extended-release quetiapine fumarate in patients with major depressive disorder.

    Science.gov (United States)

    Bauer, Michael; Thase, Michael E; Liu, Sherry; Earley, Willie; Eriksson, Hans

    2015-05-01

    Identification of predictors of treatment response in patients with major depressive disorder (MDD) may facilitate improved disease management. Data were pooled from two 6-week, double-blind, placebo-controlled studies of extended-release quetiapine (quetiapine XR; 150 or 300 mg/day) as adjunct to ongoing antidepressant therapy. Effects of psychiatric history and baseline demographic and disease characteristics on efficacy outcomes (Week 6 Montgomery Åsberg Depression Rating Scale [MADRS] total score reduction) were evaluated in population subgroups (quetiapine XR both doses pooled, n = 616; placebo, n = 303). Baseline Clinical Global Impressions-Severity (CGI-S) score and previous depressive episodes on Week 6 MADRS total score change, and baseline MADRS individual item scores on Week 6 change in CGI-Improvement score, were also evaluated. No major differences between responders and non-responders to quetiapine XR were observed for patient characteristics or demographic and disease characteristics. No suggestion of a predictive association was found between baseline CGI-S score, number of depressive episodes, and baseline MADRS item scores and efficacy outcomes. These analyses showed no major differences between responders and non-responders, and no predictive association between the parameters assessed and efficacy outcomes for adjunct quetiapine XR in patients with MDD and an inadequate response to prior antidepressant therapy.

  3. Effect of Extended-Release Niacin/Laropiprant Combination on Plasma Adiponectin and Insulin Resistance in Chinese Patients with Dyslipidaemia

    Science.gov (United States)

    Yang, Ya-Ling; Masuda, Daisaku; Yamashita, Shizuya; Tomlinson, Brian

    2015-01-01

    Objectives. This study examined whether the increase of adiponectin associated with extended-release (ER) niacin/laropiprant combination attenuates the adverse effect of niacin on glucose and insulin resistance in Hong Kong Chinese patients with dyslipidaemia. Methods. Patients (N = 121) were treated with ER niacin/laropiprant 1 g/20 mg for 4 weeks and then the dose was doubled for an additional 8 weeks. Measurements of fasting lipids, glucose, insulin, and adiponectin were performed at baseline and during the study. Results. There were significant (P < 0.001) increases in glucose (9.4 ± 13.1%), insulin (70.2 ± 91.0%), HOMA-IR (87.8 ± 103.9%), and adiponectin (169.3 ± 111.6%). The increase in adiponectin was significantly associated with increase in glucose (r = 0.221, P < 0.05), insulin (r = 0.184, P < 0.05), and HOMA-IR (r = 0.237, P < 0.01) and the association remained significant after adjustment for changes in body weight or body fat mass. Conclusion. Treatment with ER niacin/laropiprant led to a significant increase in adiponectin levels but worsening of glucose levels and insulin resistance, and the increase in adiponectin and insulin resistance were correlated suggesting the increase in adiponectin did not ameliorate the deterioration in insulin resistance. Clinical trial is registered with number on WHO-ICTRP: ChiCTR-ONC-10001038. PMID:26063948

  4. Haloperidol augmentation of fluvoxamine in skin picking disorder: a case report

    Directory of Open Access Journals (Sweden)

    Luca Maria

    2012-07-01

    Full Text Available Abstract Introduction Compulsive skin picking, being part of the broader category of impulse control disorders, is considered a residual diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. It is characterized by excessive scratching or picking of normal skin, or skin with minor surface irregularities, and occurs in 2% of patients attending dermatology clinics. Despite the clinical relevance of this disorder, no clear guidelines are available yet; clinical management is, therefore, compromised and the day-to-day clinical practice is burdened by difficulties. Studies on selective serotonin reuptake inhibitors and anti-epileptic drugs have provided limited results. The association between anti-depressants and anti-epileptics has been found to be beneficial in some impulse control disorders, but in skin picking no previous studies have been conducted on this pharmacological approach. There are very few reports on the efficacy of anti-psychotics in skin picking. Case presentation The therapeutic path described in this case report produced good results for a 59-year-old Caucasian woman. The first therapeutic approach, with fluvoxamine and oxcarbazepine was partially effective; then, the suspension of oxcarbazepine and haloperidol augmentation of fluvoxamine were adopted. After 10 weeks, a significant improvement of the disease was observed: the clinical picture and the associated symptoms were nearly solved. Conclusions To the best of our knowledge, this is the first article reporting the association of fluvoxamine and haloperidol in skin picking disorder. It might be useful to perform further research regarding the treatment of skin picking disorder: in clinical practice, several variables might limit the choice of certain drugs. Therefore, it would be useful for the clinician to be aware of other therapeutic options.

  5. Safety profile of dalfampridine extended release in multiple sclerosis: 5-year postmarketing experience in the United States

    Directory of Open Access Journals (Sweden)

    Jara M

    2015-12-01

    Full Text Available Michele Jara, Thomas Aquilina, Peter Aupperle, Adrian L Rabinowicz Acorda Therapeutics, Inc., Ardsley, NY, USA Background: Dalfampridine extended release tablets (dalfampridine-ER; prolonged-, modified, or sustained-release fampridine outside the US, 10 mg twice daily, was approved by the US Food and Drug Administration (FDA in January 2010 to improve walking in people with multiple sclerosis, as determined by an increase in walking speed. Objective: To provide a descriptive analysis of reported adverse events (AEs for commercially available dalfampridine-ER from March 2010 through March 31, 2015. Methods: Five-year postmarketing data for dalfampridine-ER were available from the exposure of approximately 107,000 patients in the US (103,700 patient-years. Commonly reported AEs (≥2% of all reported AEs and serious AEs were determined. The incidence of reported seizures was determined and the events were further investigated. Results: Among the 107,000 patients exposed to dalfampridine-ER (70% female; mean age 52.1, the most common AEs were dizziness (3.7%, insomnia (3.2%, balance disorder (3%, fall (2.4%, headache (2.4%, nausea (2.1%, and urinary tract infection (2%. Other common AEs were drug ineffectiveness (5.8%, gait disturbance (4.6%, and inappropriate dosing (3.1%. Serious AEs included rare anaphylactic reactions (five cases and drug hypersensitivity reactions (eight cases. A total of 657 seizure cases were reported (6.3/1,000 patient-years; of these, 324 were medically confirmed (3.1/1,000 patient-years. Incidence of reported seizures was stable over time. Duration of treatment prior to a seizure ranged from a single dose to >4 years; 12% of the seizures occurred within a week of starting treatment. Conclusion: The 5-year US postmarketing safety data of dalfampridine-ER is consistent with the safety profile observed in clinical trials. Incidence of reported seizures remained stable over time. Since commercial availability in March 2010, a

  6. Long-term tolerability of tolterodine extended release in children 5-11 years of age : Results from a 12-month, open-label study

    NARCIS (Netherlands)

    Nijman, Rien J. M.; Borgstein, Niels G.; Ellsworth, Pamela; Siggaard, Charlotte

    2007-01-01

    Objective: To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). Methods: This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI sugg

  7. A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents

    Science.gov (United States)

    Wagner, Karen Dineen; Redden, Laura; Kowatch, Robert A.; Wilens, Timothy E.; Segal, Scott; Chang, Kiki; Wozniak, Patricia; Vigna, Namita V.; Abi-Saab, Walid; Saltarelli, Mario

    2009-01-01

    A double-blind study that involves 150 patients aged 10-17 on the effect of divalproex extended-release in the treatment of bipolar disorder shows that the drug was similar to placebo based on adverse events and that no treatment effect was observed in the drug. The drug is not suitable for treatment of youths with bipolar I disorder, mixed or…

  8. A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex Extended-Release in the Treatment of Bipolar Disorder in Children and Adolescents

    Science.gov (United States)

    Wagner, Karen Dineen; Redden, Laura; Kowatch, Robert A.; Wilens, Timothy E.; Segal, Scott; Chang, Kiki; Wozniak, Patricia; Vigna, Namita V.; Abi-Saab, Walid; Saltarelli, Mario

    2009-01-01

    A double-blind study that involves 150 patients aged 10-17 on the effect of divalproex extended-release in the treatment of bipolar disorder shows that the drug was similar to placebo based on adverse events and that no treatment effect was observed in the drug. The drug is not suitable for treatment of youths with bipolar I disorder, mixed or…

  9. Efficacy and Safety of a Chewable Methylphenidate Extended-Release Tablet in Children with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Wigal, Sharon B; Childress, Ann; Berry, Sally A; Belden, Heidi; Walters, Faith; Chappell, Phillip; Sherman, Nancy; Orazem, John; Palumbo, Donna

    2017-05-30

    This phase 3, laboratory classroom study assessed the efficacy and safety of methylphenidate hydrochloride extended-release chewable tablets (MPH ERCT) compared with placebo in children with attention-deficit/hyperactivity disorder (ADHD). Following a 6-week, open-label, dose-optimization period, children 6-12 years of age (n = 90) with ADHD were randomly assigned to double-blind MPH ERCT at the final optimized dose (20-60 mg/day) or placebo. After 1 week of double-blind treatment, efficacy was assessed predose and 0.75, 2, 4, 8, 10, 12, and 13 hours postdose in a laboratory classroom setting. The primary efficacy measure was the average of postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores, analyzed using a mixed-model, repeated-measures analysis. Secondary efficacy measures included Permanent Product Measure of Performance (PERMP) total number of problems attempted and total number of problems correct. Safety assessments included adverse event (AE) monitoring and the Columbia-Suicide Severity Rating Scale (C-SSRS). MPH ERCT treatment statistically significantly reduced the average of all postdose SKAMP-Combined scores versus placebo (least-squares mean difference [95% confidence interval], -7.0 [-10.9, -3.1]; p 1 subject receiving MPH ERCT in the double-blind period (placebo: URTI, contusion, wound, and initial insomnia). No suicidal ideation or behavior was reported on the C-SSRS at baseline or at any postbaseline assessment. MPH ERCT 20-60 mg significantly improved ADHD symptoms compared with placebo at 2 hours postdose through at least 8 hours postdose. MPH ERCT was generally safe and well tolerated, with a safety profile consistent with other MPH ER formulations. ClinicalTrials.gov Identifier: NCT01654250. www.clinicaltrials.gov/ct2/show/NCT01654250 .

  10. Effect of the Glucagon-like Peptide-1 Analogue Exenatide Extended Release in Cats with Newly Diagnosed Diabetes Mellitus.

    Science.gov (United States)

    Riederer, A; Zini, E; Salesov, E; Fracassi, F; Padrutt, I; Macha, K; Stöckle, T M; Lutz, T A; Reusch, C E

    2016-01-01

    Exenatide extended release (ER) is a glucagon-like peptide-1 analogue that increases insulin secretion, inhibits glucagon secretion and induces satiation in humans with type 2 diabetes mellitus. The use of exenatide ER is safe and stimulates insulin secretion in healthy cats. The objective of this study is to assess the safety of exenatide ER and its effect on body weight, remission and metabolic control in newly diagnosed diabetic cats receiving insulin and a low-carbohydrate diet. Thirty client-owned cats. Prospective placebo-controlled clinical trial. Cats were treated with exenatide ER or 0.9% saline, administered SC, once weekly. Both groups received insulin glargine and a low-carbohydrate diet. Exenatide ER was administered for 16 weeks, or in cats that achieved remission it was given for 4 weeks after discontinuing insulin treatment. Nonparametric tests were used for statistical analysis. Cats in the exenatide ER and placebo groups had transient adverse signs including decreased appetite (60% vs. 20%, respectively, P = .06) and vomiting (53% vs. 40%, respectively, P = .715). Body weight increased significantly in the placebo group (P = .002), but not in cats receiving exenatide ER. Cats on exenatide ER achieved remission or good metabolic control in 40% or 89%, respectively, whereas in control cats percentages were 20% or 58% (P = .427 and P = .178, respectively). Exenatide ER is safe in diabetic cats and does not result in weight gain. Our pilot study suggests that, should there be an additional clinically relevant beneficial effect of exenatide ER in insulin-treated cats on rate of remission and good metabolic control, it would likely approximate 20% and 30%, respectively. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  11. Extended-release niacin/laropiprant significantly improves lipid levels in type 2 diabetes mellitus irrespective of baseline glycemic control

    Directory of Open Access Journals (Sweden)

    Bays HE

    2015-02-01

    Full Text Available Harold E Bays,1 Eliot A Brinton,2 Joseph Triscari,3 Erluo Chen,3 Darbie Maccubbin,3 Alexandra A MacLean,3 Kendra L Gibson,3 Rae Ann Ruck,3 Amy O Johnson-Levonas,3 Edward A O’Neill,3 Yale B Mitchel3 1Louisville Metabolic & Atherosclerosis Research Center (L-MARC, Louisville, KY, USA; 2Utah Foundation for Biomedical Research, Salt Lake City, UT, USA; 3Merck & Co, Inc., Whitehouse Station, NJ, USA Background: The degree of glycemic control in patients with type 2 diabetes mellitus (T2DM may alter lipid levels and may alter the efficacy of lipid-modifying agents. Objective: Evaluate the lipid-modifying efficacy of extended-release niacin/laropiprant (ERN/LRPT in subgroups of patients with T2DM with better or poorer glycemic control. Methods: Post hoc analysis of clinical trial data from patients with T2DM who were randomized 4:3 to double-blind ERN/LRPT or placebo (n=796, examining the lipid-modifying effects of ERN/LRPT in patients with glycosylated hemoglobin or fasting plasma glucose levels above and below median baseline levels. Results: At Week 12 of treatment, ERN/LRPT significantly improved low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C, non-high-density lipoprotein cholesterol, triglycerides, and lipoprotein (a, compared with placebo, with equal efficacy in patients above or below median baseline glycemic control. Compared with placebo, over 36 weeks of treatment more patients treated with ERN/LRPT had worsening of their diabetes and required intensification of antihyperglycemic medication, irrespective of baseline glycemic control. Incidences of other adverse experiences were generally low in all treatment groups. Conclusion: The lipid-modifying effects of ERN/LRPT are independent of the degree of baseline glycemic control in patients with T2DM (NCT00485758. Keywords: lipid-modifying agents, hyperglycemia, LDL, HDL, triglycerides

  12. Effects of once-daily extended release quetiapine fumarate on patient-reported outcomes in patients with generalized anxiety disorder

    Directory of Open Access Journals (Sweden)

    Endicott J

    2012-07-01

    Full Text Available Jean Endicott,1 Henrik Svedsäter,2 Julie C Locklear21Department of Psychiatry, Columbia University, New York, NY; 2AstraZeneca Pharmaceuticals, Wilmington, DE, USABackground: We evaluated the effects of once-daily extended-release quetiapine fumarate (quetiapine XR on patient-reported outcomes in generalized anxiety disorder (GAD.Methods: This is a report of a pooled analysis from three acute 8-week, randomized, placebo-controlled, fixed-dose (50, 150, 300 mg/day studies and a 52-week maintenance flexible dose (50–300 mg/day study of quetiapine XR monotherapy in patients with GAD. Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF percent maximum total scores (items 1–14, item 15 ("satisfaction with medication", item 16 ("overall life satisfaction", and Pittsburgh Sleep Quality Index (PSQI global scores are reported. Sheehan Disability Scale (SDS total scores were also assessed (maintenance study only.Results: The acute studies showed significant improvements at week 8 in Q-LES-Q-SF percent maximum total score with quetiapine XR 150 mg/day (P < 0.001 and item 16 with quetiapine XR 50 (P < 0.05 and 150 mg/day (P < 0.001 versus placebo; PSQI global scores significantly improved with quetiapine XR 50, 150, and 300 mg/day versus placebo (P < 0.001. The maintenance study showed significant benefits versus placebo with quetiapine XR 50–300 mg/day in Q-LES-Q-SF percent total score, item 15 and item 16 scores, PSQI global score, and SDS total score.Conclusion: Quetiapine XR 150 mg/day (acute studies and 50–300 mg/day (maintenance study improved quality of life, overall functioning, and sleep quality in patients with GAD.Keywords: atypical antipsychotic, anxiety disorders, quality of life, sleep quality, functioning, randomized studies

  13. Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures

    Directory of Open Access Journals (Sweden)

    Carol M Ulloa

    2009-09-01

    Full Text Available Carol M Ulloa, Allen Towfigh, Joseph SafdiehDepartment of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USAAbstract: Levetiracetam is a second-generation antiepileptic drug (AED with a unique chemical structure and mechanism of action. The extended release formulation of levetiracetam (Keppra XR™; UCB Pharma was recently approved by the Food and Drug Administration for adjunctive therapy in the treatment of partial-onset seizures in patients 16 years of age and older with epilepsy. This approval is based on a double-blind, randomized, placebo-controlled, multicenter, multinational trial. Levetiracetam XR allows for once-daily dosing, which may increase compliance and, given the relatively constant plasma concentrations, may minimize concentration-related adverse effects. Levetiracetam’s mode of action is not fully elucidated, but it has been found to target high-voltage, N-type calcium channels as well as the synaptic vesicle protein 2A (SV2A. Levetiracetam has nearly ideal pharmacokinetics. It is rapidly and almost completely absorbed after oral ingestion, is ‹10% protein-bound, demonstrates linear kinetics, is minimally metabolized through a pathway independent of the cytochrome P450 system, has no significant drug–drug interactions, and has a wide therapeutic index. The most common reported adverse events with levetiracetam XR were somnolence, irritability, dizziness, nausea, influenza, and nasopharyngitis. Levetiracetam XR provides an efficacious and well-tolerated treatment option for adjunctive therapy in the treatment of partial-onset seizures.Keywords: levetiracetam, partial-onset seizures, antiepileptic drugs

  14. Sustained reduction of diversion and abuse after introduction of an abuse deterrent formulation of extended release oxycodone.

    Science.gov (United States)

    Severtson, Stevan Geoffrey; Ellis, Matthew S; Kurtz, Steven P; Rosenblum, Andrew; Cicero, Theodore J; Parrino, Mark W; Gilbert, Michael K; Buttram, Mance E; Dasgupta, Nabarun; BucherBartelson, Becki; Green, Jody L; Dart, Richard C

    2016-11-01

    The development of abuse deterrent formulations is one strategy for reducing prescription opioid misuse and abuse. A putative abuse deterrent formulation of oxycodone extended release (OxyContin(®)) was introduced in 2010. Early reports demonstrated reduced abuse and diversion, however, an analysis of social media found 32 feasible methods to circumvent the abuse deterrent mechanism. We measured trends of diversion, abuse and street price of OxyContin to assess the durability of the initial reduction in abuse. Data from the Poison Center Program, Drug Diversion Program, Opioid Treatment Program, Survey of Key Informant Patients Program and StreetRx program of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS(®)) System were used. The average quarterly rates of abuse and diversion for OxyContin were compared from before reformulation to the rate in second quarter 2015. Rates were adjusted for population using US Census data and drug availability. OxyContin abuse and diversion declined significantly each quarter after reformulation and persisted for 5 years. The rate of abuse of other opioid analgesics increased initially and then decreased, but to lesser extent than OxyContin. Abuse through both oral and non-oral routes of self-administration declined following the reformulation. The geometric mean difference in the street price of reformulated OxyContin was 36% lower than the reformulated product in the year after reformulation. Despite methods to circumvent the abuse deterrent mechanism, abuse and diversion of OxyContin decreased promptly following the introduction of a crush- and solubility- resistant formulation and continued to decrease over the subsequent 5 years. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  15. Are Branded and Generic Extended-Release Ropinirole Formulations Equally Efficacious? A Rater-Blinded, Switch-Over, Multicenter Study

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    Edit Bosnyák

    2014-01-01

    Full Text Available The aim of this study was to compare the efficacy of the branded and a generic extended-release ropinirole formulation in the treatment of advanced Parkinson’s disease (PD. Of 22 enrolled patients 21 completed the study. A rater blinded to treatment evaluated Unified Parkinson’s Disease Rating Scale, Fahn-Tolosa-Marin Tremor Rating Scale, Nonmotor Symptoms Assessment Scale, and a structured questionnaire on ropinirole side effects. Besides, the patients self-administered EQ-5D, Parkinson’s Disease Sleep Scale (PDSS-2, and Beck Depression Inventories. Branded and generic ropinirole treatment achieved similar scores on all tests measuring severity of motor symptoms (primary endpoint, UPDRS-III: 27.0 versus 28.0 points, P=0.505. Based on patient diaries, the lengths of “good time periods” were comparable (10.5 and 10.0 hours for branded and generic ropinirole, resp., P=0.670. However, generic ropinirole therapy achieved almost 3.0 hours shorter on time without dyskinesia (6.5 versus. 9.5 hours, P<0.05 and 2.5 hours longer on time with slight dyskinesia (3.5 versus. 1.0 hours, P<0.05 than the branded ropinirole did. Except for gastrointestinal problems, nonmotor symptoms were similarly controlled. Patients did not prefer either formulation. Although this study has to be interpreted with limitations, it demonstrated that both generic and branded ropinirole administration can achieve similar control on most symptoms of PD.

  16. Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Ji Young Yun

    2017-01-01

    Full Text Available This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER treatment in Parkinson’s disease (PD. PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y in medication-on state, Parkinson’s disease sleep scale (PDSS, and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov.

  17. Extended release promethazine HCl using acrylic polymers by freeze-drying and spray-drying techniques: formulation considerations

    Directory of Open Access Journals (Sweden)

    Ruchi Tiwari

    2009-12-01

    Full Text Available The present study investigated a novel extended release system of promethazine hydrochloride (PHC with acrylic polymers Eudragit RL100 and Eudragit S100 in different weight ratios (1:1 and 1: 5, and in combination (0.5+1.5, using freeze-drying and spray-drying techniques. Solid dispersions were characterized by Fourier-transformed infrared spectroscopy (FT-IR, differential scanning calorimetry (DSC, Powder X-ray diffractometry (PXRD, Nuclear magnetic resonance (NMR, Scanning electron microscopy (SEM, as well as solubility and in vitro dissolution studies in 0.1 N HCl (pH 1.2, double-distilled water and phosphate buffer (pH 7.4. Adsorption tests from drug solution to solid polymers were also performed. A selected solid dispersion system was developed into capsule dosage form and evaluated for in vitro dissolution studies. The progressive disappearance of drug peaks in thermotropic profiles of spray-dried dispersions were related to increasing amount of polymers, while SEM studies suggested homogenous dispersion of drug in polymer. Eudragit RL100 had a greater adsorptive capacity than Eudragit S100, and thus its combination in (0.5+1.5 for S100 and RL 100 exhibited a higher dissolution rate with 97.14% drug release for twelve hours. Among different formulations, capsules prepared by combination of acrylic polymers using spray-drying (1:0.5 + 1.5 displayed extended release of drug for twelve hours with 96.87% release followed by zero order kinetics (r²= 0.9986.O presente trabalho compreendeu estudo de um novo sistema de liberação prolongada de cloridrato de prometazina (PHC com polímeros acrílicos Eudragit RL100 e Eudragit S100 em diferentes proporções em massa (1:1 e 1:5 e em combinação (0,5+1,5, utilizando técnicas de liofilização e de secagem por aspersão As dispersões sólidas foram caracterizadas por espectrofotometria no infravermelho por transformada de Fourier (FT-IR, calorimetria diferencial de varredura (DSC, difratometria

  18. Compression and evaluation of extended release matrix pellets prepared by the extrusion/spheronization process into disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Raveendra Pai

    2012-03-01

    Full Text Available In this study, a novel approach for compression of matrix pellets into disintegrating tablets has been studied in an attempt to overcome the issues pertaining to rupture of polymer coat during compression of reservoir-type pellets. Extended release matrix pellets were prepared by the extrusion/spheronization technique using commercially available aqueous dispersions of ethyl cellulose, acrylic polymers and sodium alginate at 10%, 20% and 30%w/w levels. Sertraline hydrochloride was used as the model drug and an in vitro release profile of 12 h was targeted. Tablets containing matrix pellets were prepared by the direct compression process. Acceptance Value, a pharmacopeial test, was applied to study the uniformity of drug distribution. Effect of compression force (2-6 kN, extrusion screen aperture size, diluent blend composition and pellet percentage on drug release and acceptance value were studied. As polymer is uniformly distributed within each pellet, the drug release pattern from uncompressed pellets was comparable to compressed tablets. Surface morphological changes due to calcium chloride treatment were observed using Scanning electron microscopy. The pellet segregated from the surface of the tablet was found to be flattened in the direction of applied compression force with minor deformities. In conclusion, matrix pellets can constitute an alternative approach to reservoir-type pellets in obtaining disintegrating tablets for extended delivery of drugs.Nesse trabalho, estudou-se nova abordagem para a compressão de matrizes de péletes em comprimidos desintegrantes, com o intuito de resolver os problemas relativos à ruptura do polímero de revestimento durante a compressão dos péletes do tipo reservatório. Matrizes de péletes de liberação estendida foram preparadas pela técnica de extrusão/esferonização, utilizando dispersões aquosas comercialmente disponíveis de etil celulose, polímeros acrílicos e alginato de sódio a 10

  19. Placebo-controlled study of fluvoxamine in the treatment of patients with compulsive buying.

    Science.gov (United States)

    Ninan, P T; McElroy, S L; Kane, C P; Knight, B T; Casuto, L S; Rose, S E; Marsteller, F A; Nemeroff, C B

    2000-06-01

    Compulsive buying is a syndrome characterized by the impulsive and/or compulsive buying of unneeded objects that results in personal distress, impairment in vocational or social functioning, and/or financial problems. Results from a two-site, double-blind, placebo-controlled 13-week trial of fluvoxamine are presented. Subjects had problematic buying behavior that they could not control for the previous 6 months or longer and met DSM-IV criteria for impulse control disorder-not otherwise specified (ICD-NOS) and the University of Cincinnati criteria for compulsive buying. Assessments included clinician-rated scales-the Yale-Brown Obsessive Compulsive Scale modified for compulsive buying, the Clinical Global Impression Scale, the Global Assessment of Functioning, and the Hamilton Rating Scale for Depression-and patient self-reports using daily diaries, which measured episodes of compulsive buying. Forty-two subjects gave informed consent, with 37 subjects providing evaluable information and 23 completing the study. Current or past psychiatric comorbidity was present in 74% of subjects. Intent-to-treat and completer analyses failed to show a significant difference between treatments on any measures of outcome. A high placebo-response rate, possibly from the behavioral benefits of maintaining a daily diary, prevents any definitive statement on the efficacy of fluvoxamine in treating compulsive buying.

  20. Intraperitoneal sertraline and fluvoxamine increase contextual fear conditioning but are without effect on overshadowing between cues.

    Science.gov (United States)

    Cassaday, H J; Thur, K E

    2015-02-01

    Treatment with selective serotonin reuptake inhibitors (SSRIs) can reduce contextual conditioning. Since contexts comprise a variety of potentially competing cues, impaired overshadowing may provide an account of such effects. The present study therefore compared the effects of two SSRIs on overshadowing and contextual conditioning, testing suppression of an ongoing behavioral response (licking) by cues previously paired with foot shock. Conditioning to a 5 s light stimulus was reduced when it was presented in compound with a 5 s noise, thus overshadowing was demonstrated. In two experiments, this overshadowing was unaffected by treatment with either sertraline or fluvoxamine. However, unconditioned suppression to the noise (tested in a control group previously conditioned to the light alone) was reduced after sertraline (10 mg/kg, i.p.). The successful demonstration of overshadowing required the use of a second conditioning session or an additional conditioning trial within the same conditioning session. Neither weak nor strong overshadowing (of the light by the tone) was affected by any drug treatment. Moreover, counter to prediction, conditioning to contextual cues was increased rather than impaired by treatment with sertraline (10 mg/kg, i.p.) and fluvoxamine (30 mg/kg, i.p.).

  1. The selective serotonin re-uptake inhibitors fluvoxamine and paroxetine differ in sexual inhibitory effects after chronic treatment.

    NARCIS (Netherlands)

    Waldinger, M.D.; Plas, A.; Pattij, T.; Oorschot, R. van; Coolen, L.M.; Veening, J.G.; Olivier, B.

    2002-01-01

    RATIONALE: The selective serotonin re-uptake inhibitors (SSRIs) delay orgasm and ejaculation in men. In men with rapid ejaculation it was shown that, of the SSRIs, paroxetine exerted the strongest delay in ejaculation and fluvoxamine the weakest. OBJECTIVES: In the present study, we compared the acu

  2. Effects of food and alcohol on the pharmacokinetics of an oral, extended-release formulation of hydrocodone in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Farr SJ

    2015-01-01

    Full Text Available Stephen J Farr,1 Cynthia Y Robinson,1 Christopher M Rubino2,3 1Zogenix, Inc., Emeryville, CA, 2Institute for Clinical Pharmacodynamics, Latham, NY, 3School of Pharmacy and Pharmaceutical Sciences, The State University of New York, University at Buffalo, Buffalo, NY, USA Background: The purpose of this study was to evaluate the pharmacokinetics, bioavailability, and safety of oral extended-release hydrocodone (HC-ER when administered with food or alcohol. Methods: Two single-center, open-label, randomized, crossover studies were conducted in healthy volunteers. In a two-period food-interaction study, 12 subjects received HC-ER 20 mg after an overnight fast and a high-fat meal. In a three-period alcohol-interaction study, 30 naltrexone-blocked subjects received HC-ER 50 mg with a 0%, 20%, or 40% alcohol/orange juice solution after an overnight fast. Pharmacokinetic parameters were derived from plasma concentrations of hydrocodone and its metabolites. Results: Exposure to hydrocodone after HC-ER 20 mg was similar in the fed and fasted states, as assessed by area under the plasma concentration versus time curve from time of dosing to time of last detectable concentration (AUC0–t; 316.14 versus 311.94 ng · h/mL; relative bioavailability (Frel was 101.74%. Differences (fed versus fasted in hydrocodone mean maximum plasma concentration (Cmax; 28.86 versus 22.74 ng/mL and median time to Cmax (tmax; 6 versus 8 hours were not clinically significant. Administration of 20% alcohol with HC-ER 50 mg did not increase systemic exposure relative to 0% alcohol (AUC0–t 878 versus 832 ng · h/mL; Frel 105% or result in clinically meaningful changes in Cmax (51.8 versus 46.3 ng/mL or tmax (5.44 versus 6.16 hours. Administration with 40% alcohol increased AUC0–t (1,008 ng · h/mL versus 832 ng · h/mL; Frel 120% and Cmax (109 versus 46.3 ng/mL, and shortened tmax (2.43 versus 6.16 hours. Adverse events occurred in 10.0%, 24.1%, and 66.7% of subjects after 0

  3. Primary care physician attitudes and perceptions of the impact of FDA-proposed REMS policy on prescription of extended-release and long-acting opioids

    Directory of Open Access Journals (Sweden)

    Salinas GD

    2012-10-01

    Full Text Available Gregory D Salinas, Caroline O Robinson, Maziar AbdolrasulniaCE Outcomes LLC, Birmingham, AL, USAAbstract: With increasing numbers of patients experiencing chronic pain, opioid therapy is becoming more common, leading to increases in concern about issues of abuse, diversion, and misuse. Further, the US Food and Drug Administration recently released a statement notifying sponsors and manufacturers of extended-release and long-acting opioids of the need to develop Risk Evaluation and Mitigation Strategies (REMS programs in order to ensure that the benefits of this therapy choice outweigh the potential risks. There is little research on physician opinions concerning opioid-prescribing and education policies. To assess attitudes surrounding new opioid policies, a survey was designed and distributed to primary care physicians in October 2011. Data collected from 201 primary care physicians show that most are not familiar with the REMS requirements proposed by the Food and Drug Administration for extended-release and long-acting opioids; there is no consensus among primary care physicians on the impact of prescribing requirements on patient education and care; and increasing requirements for extended-release and long-acting opioid education may decrease opioid prescribing. Physician attitudes toward increased regulatory oversight of opioid therapy prescriptions should be taken into consideration by groups developing these interventions to ensure that they do not cause undue burden on already busy primary care physicians.Keywords: REMS, opioids, attitudes, survey

  4. Effects of Extended-Release Niacin Added to Simvastatin/Ezetimibe on Glucose and Insulin Values in AIM-HIGH.

    Science.gov (United States)

    Goldberg, Ronald B; Bittner, Vera A; Dunbar, Richard L; Fleg, Jerome L; Grunberger, George; Guyton, John R; Leiter, Lawrence A; McBride, Ruth; Robinson, Jennifer G; Simmons, Debra L; Wysham, Carol; Xu, Ping; Boden, William E

    2016-07-01

    Niacin is an antidyslipidemic agent that may cause blood sugar elevation in patients with diabetes, but its effects on glucose and insulin values in nondiabetic statin-treated subjects with cardiovascular disease and at high risk for diabetes are less well known. This was a prespecified, intent-to-treat analysis of the Atherothrombosis Intervention in Metabolic syndrome with low high-density lipoprotein/high triglycerides: Impact on Global Health outcomes trial which randomized 3,414 participants at 92 centers in the US and Canada to extended-release niacin (ERN) plus simvastatin/ezetimibe (ERN) or simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose and insulin values were measured. Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes. In addition, nondiabetic subjects with 2 annual follow-up glucose measurements were categorized into normal, impaired fasting glucose or newly diagnosed diabetes (presumed or confirmed) states. Compared with placebo, ERN increased annual fasting glucose from baseline to 1 year in both those with normal (7.9 ± 15.8 vs 4.3 ± 10.3 mg/dL; P < .001) and impaired fasting glucose (4.1 ± 18.7 vs 1.4 ± 14.9; P < .02) and increased insulin levels. Both effects waned over the next 2 years. There were less consistent effects in those with baseline diabetes. There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose (ERN 197/336) cases (58.6%) vs placebo 135/325 cases (41.5%; P < .001) over time, but no difference in diabetes development in the 2 treatment groups except in those with normal fasting glucose at baseline. The addition of ERN to simvastatin/ezetimibe had marginal effects on glycemia in those with diabetes at baseline, and there was a trend toward increased development of new-onset diabetes. In addition, ERN increased the risk of developing impaired fasting glucose, which

  5. Prescriber utilization of dalfampridine extended release tablets in multiple sclerosis: a retrospective pharmacy and medical claims analysis

    Directory of Open Access Journals (Sweden)

    Jara M

    2014-12-01

    Full Text Available Michele Jara,1 Matthew F Sidovar,2 Herbert R Henney III2 1Drug Safety and Risk Management, 2Clinical Development and Medical Affairs, Acorda Therapeutics, Inc, Ardsley, NY, USA Purpose: This study aimed to characterize the prescribing of dalfampridine extended release (D-ER 10 mg tablet treatment in people with multiple sclerosis (MS. Methods: A retrospective cohort study was performed using Medco pharmacy and medical claims. Medical claims were used to identify MS patients with more than one prescription for D-ER with 1 year of prior continuous enrollment (n=704. These patients were matched 2:1 on age, sex, and health insurance source with a comparison group of MS patients who were treatment naïve for D-ER (n=1,403. Categorical data were analyzed by Χ2 test; ordinal data by Wilcoxon rank sum test; and continuous data by Student’s t-test. Results: Most patients were women aged 45–64 years. In the year preceding D-ER initiation, the prevalence of seizure and renal impairment was numerically lower in the D-ER cohort relative to those who were D-ER naïve (seizure: 3.1% versus 4.7%, respectively; renal impairment: 4.3% versus 5.1%, respectively; however, prescriptions for antiepileptic drugs in the two cohorts were comparable. In the year preceding treatment initiation, 62% of the D-ER cohort was prescribed MS-specific disease-modifying therapies relative to 45% who were D-ER naïve. Conclusion: Seizure and renal impairment rates among D-ER-naïve patients were consistent with published literature, yet rates among those prescribed D-ER during the year preceding treatment initiation were slightly lower than rates among D-ER-naïve patients. Given that D-ER is contraindicated in patients with history of seizure or moderate or severe renal impairment, lower rates may indicate that risk-minimization strategies contributed to the lower prevalence. Keywords: disease-modifying therapy, database, seizures, renal impairment, pharma­coepidemiology

  6. Effect of Aptensio XR (Methylphenidate HCl Extended-Release) Capsules on Sleep in Children with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Weiss, Margaret; Nordbrock, Earl; Mattingly, Greg; Wigal, Sharon; Greenhill, Laurence L.; Chang, Wei-Wei; Childress, Ann; Kupper, Robert J.; Adjei, Akwete

    2016-01-01

    Abstract Objective: To evaluate measures of sleep (exploratory endpoints) in two pivotal studies of a multilayer bead extended-release methylphenidate (MPH-MLR) treatment of attention-deficit/hyperactivity disorder in children. Methods: Study 1 evaluated the time course of response to MPH-MLR (n = 26) patients in an analog classroom setting through four phases: screening (≤28 days), open label (OL) dose optimization (4 weeks), double-blind (DB) crossover (2 weeks; placebo vs. optimized dose), and follow-up call. Study 2 was a forced-dose parallel evaluation of MPH-MLR (n = 230) in four phases: screening (≤28 days), DB (1 week; placebo or MPH-MLR 10, 15, 20, or 40 mg/day), OL dose optimization (11 weeks), and follow-up call. Sleep was evaluated by parents using the Children's or Adolescent Sleep Habits Questionnaire (CSHQ or ASHQ) during the DB and OL phases. DB analysis: Study 1 (crossover), analysis of variance; Study 2, analysis of covariance. OL analysis: paired t-test. Results: DB: treatments were significantly different in Study 1 only for CSHQ Sleep Onset Delay (MPH-MLR, 1.90 vs. placebo, 1.34; p = 0.0046, placebo was better), and Study 2 for CSHQ Parasomnias (treatment, p = 0.0295), but no MPH-MLR treatment was different from placebo (pairwise MPH-MLR treatment to placebo, all p ≥ 0.170). OL: CSHQ total and Bedtime Resistance, Sleep Duration, Sleep Anxiety, Night Wakings, Parasomnias, and Sleep-disordered Breathing subscales decreased (improved, Study 1) significant only for CSHQ Night Wakings (p Parasomnias, and Daytime Sleepiness, and ASHQ total, Bedtime, Sleep Behavior, and Morning Waking all significantly improved (p < 0.05). Conclusions: In both studies, there was minimal negative impact of MPH-MLR on sleep during the brief DB phase and none during the longer duration OL phase. Some measures of sleep improved with optimized MPH-MLR dose. PMID:27754700

  7. The social functional outcome of being naturalistically treated with paliperidone extended-release in patients with schizophrenia

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    Nakagawa R

    2015-06-01

    Full Text Available Ryoko Nakagawa,1 Takashi Ohnishi,1 Hisanori Kobayashi,1 Akihide Wakamatsu,2 Ai Tanimura,3 Kazuo Morita,3 Toshio Yamaoka,3 Hideo Usui,3 Yoshimasa Ogawa,3 Akiko Fujino,3 Kazutake Yoshizawa11Evidence Generation Department, Medical Affairs Division, 2Medical Affairs Strategy Department, Medical Affairs Division, 3Drug Safety Surveillance Department, Japan Safety and Surveillance Division, Janssen Pharmaceutical K.K., Tokyo, JapanBackground: Social functioning is an important outcome for patients with schizophrenia. To evaluate the effects of paliperidone extended-release (PAL-ER on social function, symptomatology, and safety in the routine clinical practice, we conducted a 1-year post-marketing surveillance study of PAL-ER. We also explored relationships between symptomatic improvement and socially functional outcome in patients with schizophrenia.Patients and methods: Patients with an established diagnosis of schizophrenia were allowed flexible 3–12 mg/day dosing during the surveillance. Patients were assessed on social functioning using the Social and Occupational Functioning Assessment Scale (SOFAS and on symptomatology using the Clinical Global Impression–Schizophrenia scale. All adverse events (AEs were also collected.Results: A total of 1,429 patients were enrolled in the surveillance study, of whom 1,405 were evaluable for safety and 1,142 were evaluable for efficacy. The treatment discontinuation rate for any reason during the observation period was 34.66%. Significant improvements were observed on both Social and Occupational Functioning Assessment Scale and Clinical Global Impression–Schizophrenia scale during the observation period. The percentage of patients with socially functional remission (SOFAS ≥61 also increased significantly. A significant association between early improvements in positive symptoms, sex, severity of negative symptoms at baseline, and socially functional remission was observed. A total of 33.52% of patients

  8. Treatment patterns and health care resource utilization associated with dalfampridine extended release in multiple sclerosis: a retrospective claims database analysis

    Directory of Open Access Journals (Sweden)

    Guo A

    2016-05-01

    Full Text Available Amy Guo,1 Michael Grabner,2 Swetha Rao Palli,2 Jessica Elder,1 Matthew Sidovar,1 Peter Aupperle,1 Stephen Krieger3 1Acorda Therapeutics Inc., Ardsley, New York, NY, USA; 2HealthCore Inc., Wilmington, DE, USA; 3Corinne Goldsmith Dickinson Center for MS, Icahn School of Medicine at Mount Sinai, New York, NY, USA Background: Although previous studies have demonstrated the clinical benefits of dalfampridine extended release (D-ER tablets in patients with multiple sclerosis (MS, there are limited real-world data on D-ER utilization and associated outcomes in patients with MS. Purpose: The objective of this study was to evaluate treatment patterns, budget impact, and health care resource utilization (HRU associated with D-ER use in a real-world setting. Methods: A retrospective claims database analysis was conducted using the HealthCore Integrated Research DatabaseSM. Adherence (measured by medication possession ratio, or [MPR] and persistence (measured by days between initial D-ER claim and discontinuation or end of follow-up were evaluated over 1-year follow-up. Budget impact was calculated as cost per member per month (PMPM over the available follow-up period. D-ER and control cohorts were propensity-score matched on baseline demographics, comorbidities, and MS-related resource utilization to compare walking-impairment-related HRU over follow-up. Results: Of the 2,138 MS patients identified, 1,200 were not treated with D-ER (control and 938 were treated with D-ER. Patients were aged 51 years on average and 74% female. Approximately 82.6% of D-ER patients were adherent (MPR >80%. The estimated budget impact range of D-ER was $0.014–$0.026 PMPM. Propensity-score-matched D-ER and controls yielded 479 patients in each cohort. Postmatching comparison showed that the D-ER cohort was associated with fewer physician (21.5% vs 62.4%, P<0.0001 and other outpatient visits (22.8% vs 51.4%, P<0.0001 over the 12-month follow-up. Changes in HRU from follow

  9. Spray drying as a fast and simple technique for the preparation of extended release dipyridamole (DYP) microparticles in a fixed dose combination (FDC) product with aspirin.

    Science.gov (United States)

    Hamishehkar, H; Valizadeh, H; Alasty, P; Monajjemzadeh, F

    2014-02-01

    Recent advances have proven that the combinational therapy of extended release dipyridamole (DYP) and fast release aspirin (ASP) can improve clinical indices of heart failure in several vascular disorders. Although pharmaceutical industries always supported fast, simple and cost saving techniques in their productions, there is no simple reported method available for this purpose. The aim of this study was to check the possibility of preparing a FDC product, containing individual dosage units of extended release DYP microparticles and fast release ASP, using the spray-drying technique as a practice compatible with pharmaceutical industries. Solid dispersions of DYP in different polymeric substances (ethyl cellulose, carnauba wax, and Eudragit PO 100), were prepared using the spray-drying method. The physicochemical properties and structure of the prepared microparticles were analyzed using different techniques, such as the particle size analyzer (PSA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X ray diffraction (XRD), and USP dissolution tester. ASP tablets were prepared individually and tested according to pharmacopeia. Results showed that prepared microparticles measured about 2.3 µm in size. Statistical analysis of the release data revealed that there is no significant difference in the mean release amount of the selected formulation compared to the innovative brand (Aggrenox®). Findings proposed a new formulation (F7) as an alternative to innovative brand and proved spray drying as a practice compatible with pharmaceutical industries and as a successful method for sustaining the DYP release rate from prepared microparticles in a FDC dosage form. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Cost-Effectiveness of Extended-Release Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder Sub-Optimally Treated with Immediate Release Methylphenidate

    NARCIS (Netherlands)

    van der Schans, Jurjen; Kotsopoulos, Niko; Hoekstra, Pieter J.; Hak, Eelko; Postma, Maarten J.

    2015-01-01

    BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric disorder in children and adolescents. Immediate-release methylphenidate (IR-MPH) is the medical treatment of first choice. The necessity to use several IR-MPH tablets per day and associated potential social stigma at

  11. Design and in vitro evaluation of a novel controlled onset extended-release delivery system of metoprolol tartrate

    Directory of Open Access Journals (Sweden)

    Jaber Emami

    2016-01-01

    Full Text Available Blood pressure rises rapidly upon awakening and maybe responsible, in part, for the increased incidence of myocardial infarction and stroke during the morning hours. The aim of the present study was, therefore, to develop a novel chronotherapeutic formulation of metoprolol tartrate (MT for night time dosing providing maximum effect in the morning hours. Core tablets contained MT, sodium chloride, lactose, Avicel ® and starch. Powders were mixed, sieved and directly compressed in to tablets using a single punch tablet machine. Core tablets were then coated with 5 or 10% hydroxypropyl methylcellulose as swelling layer and subsequently outer membrane with the mixture of various ratios of Eudragit ® RS to RL at different coating levels 5, 10, 15% as semi-permeable water insoluble outer coat by conventional pan-spray method. The best formulation with regard to release behavior was chosen and subjected to further release studies in various rotational speed and pHs. Both lag time and release rate were dependent on the coating levels and the osmotic pressure of dissolution medium. A linear relationship between lag time and outer coating levels was observed. The lag time was prolonged with an increase in the coating levels. Both diffusion and osmotic pumping effect were involved in drug release from the device. Significant increases in drug release behavior was not observed using dissolution medium with various pH and different agitation rates. It was found that the release rate was independent of pH, rotational speed and gastric motility and may not be altered due to changes of pH and peristaltic movement along the GI tract.

  12. Development and validation of an in vitro–in vivo correlation (IVIVC model for propranolol hydrochloride extended-release matrix formulations

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    Chinhwa Cheng

    2014-06-01

    Full Text Available The objective of this study was to develop an in vitro–in vivo correlation (IVIVC model for hydrophilic matrix extended-release (ER propranolol dosage formulations. The in vitro release characteristics of the drug were determined using USP apparatus I at 100 rpm, in a medium of varying pH (from pH 1.2 to pH 6.8. In vivo plasma concentrations and pharmacokinetic parameters in male beagle dogs were obtained after administering oral, ER formulations and immediate-release (IR commercial products. The similarity factor f2 was used to compare the dissolution data. The IVIVC model was developed using pooled fraction dissolved and fraction absorbed of propranolol ER formulations, ER-F and ER-S, with different release rates. An additional formulation ER-V, with a different release rate of propranolol, was prepared for evaluating the external predictability. The results showed that the percentage prediction error (%PE values of Cmax and AUC0–∞ were 0.86% and 5.95%, respectively, for the external validation study. The observed low prediction errors for Cmax and AUC0–∞ demonstrated that the propranolol IVIVC model was valid.

  13. 76 FR 43330 - Notice of Release of the Exposure Draft of Technical Bulletin 2011-2, Extended Deferral of the...

    Science.gov (United States)

    2011-07-20

    ... From the Federal Register Online via the Government Publishing Office FEDERAL ACCOUNTING STANDARDS... the Effective Date of Technical Bulletin 2006-1 AGENCY: Federal Accounting Standards Advisory Board... given that the Federal Accounting Standards Advisory Board (FASAB) has released the Exposure Draft...

  14. A novel subcutaneous controlled-release amoxicillin degradable implant for extended-interval administration in veterinary medicine.

    Science.gov (United States)

    Horwitz, E; Kagan, L; Avni-Magen, N; Daryi, D; Gati, I; Hoffman, A; Friedman, M; Lavy, E

    2011-10-01

    Dosage forms of antimicrobials play a critical role in facilitating the attainment of pharmacokinetic-pharmacodynamic (PK-PD) targets as well as adherence in both veterinary and human medicine. The purpose of this study was to develop and evaluate a controlled-release subcutaneous amoxicillin implant for single-dose therapy of large ruminants such as goats, sheep, and deer. The degradable implant, designed to attain PK-PD targets following single administration, was evaluated for amoxicillin release rate and time-concentration profile. In vitro release studies demonstrated constant-rate release of approximately 40% of amoxicillin content within 96 h. In an in vivo study in goats, serving as a model for target animals, a serum concentration of approximately 0.4 mg/L was achieved within 8 h of implant insertion and maintained for >6 days. In comparison, in control goats given a standard single intramuscular amoxicillin dose of 15 mg/kg, amoxicillin peaked at 1.2 mg/L after 1 h, rapidly dropping to below detection level at 8 h. These results suggest that the proposed implant offers a unique modality for animal caregivers to conveniently administer a full antimicrobial course following a single dose of an efficient PK-PD-optimized dosage form. Furthermore, modifications of implant composition may allow for tailoring of its characteristics to various PK, PD, microbiological, and clinical requirements. © 2010 Blackwell Publishing Ltd.

  15. Spectrophotometric study for the reaction between fluvoxamine and 1,2-naphthoquinone-4-sulphonate: Kinetic, mechanism and use for determination of fluvoxamine in its dosage forms

    Science.gov (United States)

    Darwish, Ibrahim A.; Abdine, Heba H.; Amer, Sawsan M.; Al-Rayes, Lama I.

    2009-05-01

    Spectrophotometric study was carried out, for the first time, to investigate the reaction between the antidepressant fluvoxamine (FXM) and 1,2-naphthoquinone-4-sulphonate (NQS) reagent. In alkaline medium (pH 9), an orange-colored product exhibiting maximum absorption peak ( λmax) at 470 nm was produced. The kinetics of the reaction was investigated and its activation energy was found to be 2.65 kcal mol -1. Because of this low activation energy, the reaction proceeded easily. The stoichiometry of the reaction was determined and the reaction mechanism was postulated. This color-developing reaction was successfully employed in the development of simple and rapid spectrophotometric method for determination of FXM in its pharmaceutical dosage forms. Under the optimized reaction conditions, Beer's law correlating the absorbance ( A) with FXM concentration ( C) was obeyed in the range of 0.6-8 μg ml -1. The regression equation for the calibration data was A = 0.0086 + 0.1348 C, with good correlation coefficient (0.9996). The molar absorptivity ( ɛ) was 5.9 × 10 4 l mol -1 cm -1. The limits of detection and quantification were 0.2 and 0.6 μg ml -1, respectively. The precision of the method was satisfactory; the values of relative standard deviations did not exceed 2%. The proposed method was successfully applied to the determination of FXM in its pharmaceutical tablets with good accuracy and precisions; the label claim percentage was 100.47 ± 0.96%. The results obtained by the proposed method were comparable with those obtained by the official method. The proposed method is superior to all the previously reported spectrophotometric methods for determination of FXM in terms of its simplicity and sensitivity. The method is practical and valuable for its routine application in quality control laboratories for analysis of FXM.

  16. Development and validation of a stability-indicating LC method for the determination of venlafaxine in extended-release capsules and dissolution kinetic studies.

    Science.gov (United States)

    Bernardi, Larissa S; Oliveira, Paulo R; Murakami, Fábio S; Borgmann, Silvia H M; Arend, Marcela Z; Cardoso, Simone G

    2009-10-01

    A stability-indicating reversed-phase high-performance liquid chromatography method is developed and validated for the determination of venlafaxine hydrochloride (VEN) in extended-release capsules containing spherical beads and for dissolution studies. The method is carried out on a Luna C(18) column (250 mm x 4.6 mm) maintained at 35 degrees C. The mobile phase is composed of ammonium-acetate buffer 32 mM, adjusted to pH 6.8 with phosphoric acid-acetonitrile-methanol (62:30:8, v/v/v), run at a flow rate of 1.0 mL/min, and detection at 226 nm. Validation parameters such as the specificity, linearity, precision, accuracy, and robustness are evaluated, giving results within the acceptable range. In order to evaluate the best dissolution condition, the dissolution profiles are performed under different conditions, such as media (HCl, water, phosphate buffer), apparatus (I and II), and dissolution rates (50, 75, and 100 rpm). The kinetics release mechanism is evaluated by fitting different models, such as the zero order rate, first order, and Higuchi. Moreover, the proposed method is successfully applied for the assay of VEN in extended-release capsules.

  17. Gene expression changes in peripheral mononuclear cells from schizophrenic patients treated with a combination of antipsychotic with fluvoxamine.

    Science.gov (United States)

    Chertkow, Yael; Weinreb, Orly; Youdim, Moussa B H; Silver, Henry

    2007-10-01

    Antipsychotic treatment combined with Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant can improve negative symptoms in schizophrenic patients that are unresponsive to antipsychotic drugs alone. The mechanism of this therapeutic effect is not clear. The current study examined molecular changes induced by the combined treatment in human peripheral mononuclear cells (PMC) in order to get insight into its mechanism of action. Gene expression profile of PMC from antipsychotic-treated patients was examined before addition of the SSRI fluvoxamine, and 3 and 6 weeks after. Gene expression patterns screened with a cDNA array, comprising 1176 genes, revealed homologous changes in a range of transcripts related to G-protein coupled receptors (GPCR). Genes related to GPCR-family were assayed using customized cDNA array and the results verified by real-time RT-PCR. The mRNA expression of chemokine receptors, IL8RA and CCR1, and of RGS7 was significantly down-regulated following fluvoxamine augmentation. The clinical assessments showed improvement in negative symptoms following the combined treatment. The transcriptional analysis suggests that the therapeutic mechanism of the combined antipsychotic-fluvoxamine treatment may involve genes associated with G-protein coupled receptors (GPCR). Our findings suggest that gene expression changes in PMC may be useful in investigating the mechanism of drug action in schizophrenia.

  18. From selective to highly selective SSRIs: a comparison of the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram.

    Science.gov (United States)

    Schreiber, Shaul; Pick, Chaim G

    2006-08-01

    Most Serotonin Selective Reuptake Inhibitors (SSRIs) have been found to possess secondary binding properties, while citalopram and its S-enantiomer (escitalopram) have been reconfirmed "purest SSRIs". Using the mouse model of acute pain hotplate analgesia meter, we evaluated the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram, injected i.p. Fluvoxamine induced a dose-dependent clear antinociceptive effect (with an ED(50) value of 6.4 mg/kg). Both fluoxetine and citalopram induced (separately) only a weak antinociceptive effect with an inverse "U" shape curve. All three drug's effects were not abolished by naloxone. Escitalopram did not elicit any effect at quasi-equipotent doses. These findings show that fluoxetine, fluvoxamine and citalopram given i.p. are weak antinociceptors, (not mediated through opioid mechanisms), while escitalopram possesses no antinociceptive properties when injected i.p. This difference between citalopram and escitalopram calls for further studies in order to assess the various differences between the two enantiomers of citalopram, and between each enantiomer and the racemic mixture.

  19. Dopamine dysregulation syndrome in Parkinson's disease patients with unsatisfactory switching from immediate to extended release pramipexole: a further clue to incentive sensitization mechanisms?

    Science.gov (United States)

    Solla, Paolo; Cannas, Antonino; Corona, Marta; Marrosu, Maria Giovanna; Marrosu, Francesco

    2013-01-01

    A small proportion of patients with Parkinson's disease (PD), chronically under dopamine replacement therapy, may undergo an addiction-like behavioral disturbance, named dopamine dysregulation syndrome (DDS). This behavioral disorder is characterized by the increase of doses beyond those required for motor control, and its management remains difficult; thus, early recognition and careful monitoring of at-risk individuals are crucial. We report the cases of two PD patients with a previous unsatisfactory switching from an immediate release (IR) to an extended release (ER) pramipexole formulation who developed DDS. PD patients unsatisfactorily switched from an IR to an ER formulation of dopamine agonists should be considered as at-risk individuals for DDS development.

  20. Glycine-extended gastrin enhances somatostatin release from cultured rabbit fundic D-cells [v1; ref status: indexed, http://f1000r.es/8n

    Directory of Open Access Journals (Sweden)

    Ian LP Beales

    2013-02-01

    Full Text Available The role of the peptide hormone gastrin in stimulating gastric acid secretion is well established. Mature amidated gastrin is processed from larger peptide precursor forms. Increasingly these processing intermediates, such as glycine-extended gastrin (G-Gly and progastrin, have been shown to have biological activities of their own, often separate and complementary to gastrin. Although G-Gly is synthesized and secreted by gastric antral G-cells, the physiological functions of this putative mediator are unclear. Gastrin and cholecystokinin (CCK stimulate the secretion of somatostatin from gastric D-cells as part of the feedback control of gastric acid. In this study the effect of G-Gly and gastrin on the release of somatostatin from rabbit fundic D-cells was examined. D-cells were obtained by collagenase-EDTA digestion and elutriation and cultured for 48 hours. With a 2 hour exposure to the peptides, gastrin but not G-Gly stimulated somatostatin release. Treatment of D-cells for 24 hours with gastrin or G-Gly individually, significantly enhanced subsequent basal as well as CCK- and GLP-1-stimulated somatostatin release. Twenty four hours exposure to gastrin combined with G-Gly synergistically enhanced basal and agonist-stimulated somatostatin release and cellular somatostatin content. Gastrin and G-Gly may be important in the longer term regulation of D-cell function.

  1. Development of in vitro-in vivo correlation for extended-release niacin after administration of hypromellose-based matrix formulations to healthy volunteers.

    Science.gov (United States)

    Kesisoglou, Filippos; Rossenu, Stefaan; Farrell, Colm; Van Den Heuvel, Michiel; Prohn, Marita; Fitzpatrick, Shaun; De Kam, Pieter-Jan; Vargo, Ryan

    2014-11-01

    Development of in vitro-in vivo correlations (IVIVCs) for extended-release (ER) products is commonly pursued during pharmaceutical development to increase product understanding, set release specifications, and support biowaivers. This manuscript details the development of Level C and Level A IVIVCs for ER formulations of niacin, a highly variable and extensively metabolized compound. Three ER formulations were screened in a cross-over study against immediate-release niacin. A Multiple Level C IVIVC was established for both niacin and its primary metabolite nicotinuric acid (NUA) as well as total niacin metabolites urinary excretion. For NUA, but not for niacin, Level A IVIVC models with acceptable prediction errors were achievable via a modified IVIVC rather than a traditional deconvolution/convolution approach. Hence, this is in contradiction with current regulatory guidelines that suggest that when a Multiple Level C IVIVC is established, Level A models should also be readily achievable. We demonstrate that for a highly variable, highly metabolized compound such as niacin, development of a Level A IVIVC model fully validated according to agency guidelines may be challenging. However, Multiple Level C models are achievable and could be used to guide release specifications and formulation/manufacturing changes.

  2. Comparison Of Effect Of Addition Of Fluvoxamine Or Risperidone To Clozapine In Chronic Partially Responsive Schizophrenic Patients On Clinical Response, QTc interval And Lipid profile

    Directory of Open Access Journals (Sweden)

    Sunil Mahakalkar

    2016-07-01

    Full Text Available Objective – To study & compare the augmentation effect of addition of fluvoxamine or risperidone in chronic partially responsive schizophrenic patients receiving clozapine on clinical and laboratory parameters.Methods - A prospective, randomized, parallel, open label 12 weeks study. The schizophrenic patients, aged 20-60 years, who followed the DSM-IV diagnostic criteria and receiving clozapine therapy, showing partial response to the treatment were recruited and the study was carried out from January 2007 to June 2008. Subjects were randomized into two groups: Group A (n=28: fluvoxamine (25-50mg/day was added to clozapine (25-200mg/day & Group B (n=27: risperidone (1-5mg/day was added to clozapine therapy. The effect of drugs was assessed by PANSS, BPRS scale and ECG and lipid profile were done at 6 and 12 weeks.Result - There was significant decrease in PANSS and BPRS score in both groups.Fluvoxamine + clozapine significantly reduced PANSS score as compared to risperidone + clozapine compared to baseline and between 6 and 12 weeks. Risperidone +clozapine prolonged QTc interval (at 12 weeks and elevated serum TG, VLDL, HDL significantly at 6 and 12 weeks.Conclusion – Although addition of fluvoxamine and risperidone to clozapine are effective in management of chronic partially responsive schizophrenia on clozapine, fluvoxamine is more effective as well as safer compared to Risperidone when compared for 6 and 12 weeks in these patients.

  3. Effect of fluvoxamine on platelet 5-HT2A receptors as studied by [3H]lysergic acid diethylamide ([3H]LSD) binding in healthy volunteers.

    Science.gov (United States)

    Spigset, O; Mjörndal, T

    1997-09-01

    Alterations in platelet 5-HT2A receptor characteristics have been reported in major depression as well as in other psychiatric diseases, and some effort has been made to utilize platelet 5-HT2A receptor status as a biological correlate to antidepressant drug response. In order to investigate whether treatment with a selective serotonin reuptake inhibitor affects platelet 5-HT2A receptors, we have studied platelet [3H]lysergic acid diethylamide ([3H]LSD) binding in healthy subjects treated with fluvoxamine in increasing dosage once weekly for 4 weeks. After 1 week of fluvoxamine treatment (25 mg/day), both Bmax and Kd were significantly lower than before the start of the treatment (19.9 versus 25.5 fmol/mg protein, P = 0.005 for Bmax; 0.45 versus 0.93 nM, P = 0.006 for Kd). Bmax returned to baseline during week 2, whereas Kd was lower than the baseline value throughout the treatment period. After discontinuation of fluvoxamine treatment, there was a significant increase in Kd (0.50 nM before discontinuation vs. 1.14 nM after discontinuation; P = 0.001), but not in Bmax. The study demonstrates that fluvoxamine affects platelet 5-HT2A receptor status irrespective of underlying psychiatric disease, and that this effect is evident already after 1 week at a subtherapeutic fluvoxamine dose.

  4. Validated HPLC method for the pharmacokinetic study of oral extended-release cefpodoxime proxetil chitosan-alginate beads in rabbits.

    Science.gov (United States)

    Mujtaba, Ali; Kohli, Kanchan

    2017-05-01

    The aim of this study is to develop a simple and applicable HPLC method for the detection of cefpodoxime acid (CFA) in rabbit plasma after oral administration of cefpodoxime proxetil (CFP) loaded chitosan-alginate (CH-ALG) beads formulation. CFP is a prodrug that is deesterified in vivo to its active metabolite CFA to exhibit antibiotic activity. Chromatographic separation of CFA and internal standard (IS) was achieved by a RP18(C18), Phenomenax®100, (250×4.6mm) with the mobile phase consisting of (0.02mol/l (20mM) ammonium acetate solution and acetonitrile (92:8, v/v, pH=4.6) at a flow rate of 1.0ml/min. The method was validated according to the requirements of US-FDA guidelines for bioanalytical method validation. The linear regression analysis for the calibration plots showed good linear relationship (R(2)=0.9905) in the working concentration range of 0.5-50μg/ml. The limits of detection and quantification (S/N=3) were 0.069 and 0.136μg/ml. Plasma CFA levels were successfully determined in rabbit with satisfactory precision and accuracy. The analyte was found to be stable after a number of stability studies. The proposed HPLC method was successfully applied to pharmacokinetic study in rabbits for CFP loaded CH-ALG beads and marketed immediate release (IR) tablets. All pharmacokinetic parameters were assessed.

  5. Individualized, discrete event, simulations provide insight into inter- and intra-subject variability of extended-release, drug products

    Directory of Open Access Journals (Sweden)

    Kim Sean HJ

    2012-08-01

    Full Text Available Abstract Objective Develop and validate particular, concrete, and abstract yet plausible in silico mechanistic explanations for large intra- and interindividual variability observed for eleven bioequivalence study participants. Do so in the face of considerable uncertainty about mechanisms. Methods We constructed an object-oriented, discrete event model called subject (we use small caps to distinguish computational objects from their biological counterparts. It maps abstractly to a dissolution test system and study subject to whom product was administered orally. A subject comprises four interconnected grid spaces and event mechanisms that map to different physiological features and processes. Drugs move within and between spaces. We followed an established, Iterative Refinement Protocol. Individualized mechanisms were made sufficiently complicated to achieve prespecified Similarity Criteria, but no more so. Within subjects, the dissolution space is linked to both a product-subject Interaction Space and the GI tract. The GI tract and Interaction Space connect to plasma, from which drug is eliminated. Results We discovered parameterizations that enabled the eleven subject simulation results to achieve the most stringent Similarity Criteria. Simulated profiles closely resembled those with normal, odd, and double peaks. We observed important subject-by-formulation interactions within subjects. Conclusion We hypothesize that there were interactions within bioequivalence study participants corresponding to the subject-by-formulation interactions within subjects. Further progress requires methods to transition currently abstract subject mechanisms iteratively and parsimoniously to be more physiologically realistic. As that objective is achieved, the approach presented is expected to become beneficial to drug development (e.g., controlled release and to a reduction in the number of subjects needed per study plus faster regulatory review.

  6. Minimal Clinically Important Difference in Parkinson’s Disease as Assessed in Pivotal Trials of Pramipexole Extended Release

    Directory of Open Access Journals (Sweden)

    Robert A. Hauser

    2014-01-01

    Full Text Available Background. The minimal clinically important difference (MCID is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson’s Disease Rating Scale (UPDRS scores in early Parkinson’s disease (EPD and for UPDRS scores and “OFF” time in advanced Parkinson’s disease (APD. Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of pramipexole ER that included pramipexole immediate release (IR as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves “a little better” on patient global impression of improvement (PGI-I minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (pramipexole ER, pramipexole IR for UPDRS II were −1.8 and −2.0, for UPDRS III −6.2 and −6.1, and for UPDRS II + III −8.0 and −8.1. MCIDs in APD for UPDRS II were −1.8 and −2.3, for UPDRS III −5.2 and −6.5, and for UPDRS II + III −7.1 and −8.8. MCID for “OFF” time (pramipexole ER, pramipexole IR was −1.0 and −1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials.

  7. A long-term, open-label safety study of single-entity hydrocodone bitartrate extended release for the treatment of moderate to severe chronic pain

    Directory of Open Access Journals (Sweden)

    Nalamachu S

    2014-11-01

    Full Text Available Srinivas Nalamachu,1,2 Richard L Rauck,3 Martin E Hale,4 Orlando G Florete Jr,5 Cynthia Y Robinson,6 Stephen J Farr,6 1International Clinical Research Institute, Overland Park, KS, USA; 2Kansas University Medical Center, Kansas City, KS, USA; 3Carolinas Pain Institute, Center for Clinical Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 4Gold Coast Research, LLC, Weston, FL, USA; 5Institute of Pain Management, Jacksonville, FL, USA; 6Zogenix, Inc., Emeryville, CA, USA Objective: To evaluate the long-term safety, tolerability, and effectiveness of single-entity extended-release hydrocodone in opioid-experienced subjects with moderate to severe chronic pain not receiving adequate pain relief or experiencing intolerable side effects from their current opioid. Methods: This multicenter, open-label study started with a conversion/titration phase (≤6 weeks where subjects (n=638 were converted to individualized doses (range 20–300 mg of extended-release hydrocodone dosed every 12 hours, followed by a 48-week maintenance phase (n=424. The primary objective (safety and tolerability and the secondary objective (long-term efficacy as measured by change in average pain score; 0= no pain, 10= worst imaginable pain were monitored throughout the study. Results: Subjects were treated for a range of chronic pain etiologies, including osteoarthritis, low back pain, and neuropathic and musculoskeletal conditions. The mean hydrocodone equivalent dose at screening was 68.9±62.2 mg/day and increased to 139.5±81.7 mg/day at the start of the maintenance phase. Unlimited dose adjustments were permitted at the investigator's discretion during the maintenance phase, reflecting typical clinical practice. No unexpected safety issues were reported. Common adverse events during the conversion/titration and maintenance phases, respectively, were constipation (11.3% and 12.5%, nausea (10.7% and 9.9%, vomiting (4.1% and 9.7%, and somnolence (7

  8. Compound Metformin/Glipizide Bilayer Extended Release Tablets: Development and in Vitro Release%复方二甲双胍/格列吡嗪双层缓释片:设计与体外释放

    Institute of Scientific and Technical Information of China (English)

    欧阳德方; 聂淑芳; 孟晋; 杨星钢; 宋志全; 潘卫三

    2005-01-01

    Aim In this study, compound metformin/glipizide bilayer extended release tablets were formulated with hydroxypropyl methylcellulose (HPMC) by wet granulation technique in order to tackle the problems associated with the multidrug therapy of non-insulin dependent diabetes mellitus. Methods High-dose metformin is difficult to formulate into a tablet dosage form due to its poor compressibility and compactibility. In this study, the way to overcome the difficulty was to utilize stearic alcohol to prepare the tablet formulation. The influences of viscosity, amount of HPMC, and weight of fillers were investigated. The optimal formulation had acceptable physicochemical properties and released metformin and glipizide over 10 h. Results The data of metformin obtained from in vitro release fitted Higuchi kinetics best, while the release of glipizide in vitro was found to follow zero kinetics. Conclusion Compound metformin/glipizide bilayer extended release tablets have been successfully developed.%目的本文为了解决2型糖尿病中的多药治疗问题,用HPMC进行湿法制粒制备了复方二甲双胍/格列吡嗪双层缓释片.方法由于二甲双胍的压缩成型性较差,高剂量的二甲双胍很难压制成片.在实验中,采用十八醇克服了这一问题.研究了HPMC的黏度、用量和填充剂的用量对药物释放的影响.优化的处方具有较好的物理化学性质,其中二甲双胍和格列吡嗪缓释时间为10小时.结果二甲双胍的体外释放符合Higuchi方程, 而格列吡嗪的体外释放符合零级方程.结论本文成功地设计了一种新型的复方二甲双胍/格列吡嗪双层缓释片.

  9. Comparison of pharmacokinetic variability of fesoterodine vs. tolterodine extended release in cytochrome P450 2D6 extensive and poor metabolizers.

    Science.gov (United States)

    Malhotra, Bimal; Darsey, Edress; Crownover, Penelope; Fang, Juanzhi; Glue, Paul

    2011-08-01

    Tolterodine and 5-hydroxymethyl tolterodine (5-HMT) are equipotent active moieties of tolterodine; 5-HMT is the singular active moiety of fesoterodine. The formation of 5-HMT from tolterodine occurs via CYP2D6, and some subjects are poor metabolizers CYP2D6. On the other hand, the formation of 5-HMT from fesoterodine occurs via ubiquitous esterases. Cross-study comparisons of data from phase 1 studies suggest that active moiety exposures are considerably more variable following tolterodine extended release vs. fesoterodine. This head-to-head study confirmed the findings of reduced pharmacokinetic variability of fesoterodine and further delineates that tolterodine, and not 5-HMT, was the principal source of variability after administration of tolterodine extended release. The data suggest that fesoterodine delivers 5-HMT consistently, regardless of CYP2D6 status, with up to 40% higher bioavailability compared with tolterodine. Tolterodine and 5-hydroxymethyl tolterodine (5-HMT) are equipotent active moieties of tolterodine; 5-HMT is the singular active moiety of fesoterodine. Formation of 5-HMT from fesoterodine and tolterodine occurs via esterases and CYP2D6 respectively. This randomized, crossover, open-label, multiple-dose study in CYP2D6 extensive metabolizers (EMs) and poor metabolizers (PMs) compared the pharmacokinetics of fesoterodine vs. tolterodine extended release (ER). Subjects received fesoterodine and tolterodine ER with a ≥3-day washout period. Treatment comprised 4-mg once daily doses for 5 days escalated to 8-mg once daily for 5 days. Pharmacokinetics of active moieties were compared by drug, dose and genotype. Active moiety exposures following fesoterodine and tolterodine ER increased proportional to dose in EMs and PMs. In EMs only, coefficients of variation for AUC and C(max) following fesoterodine (up to 46% and 48% respectively) were lower than those following tolterodine ER (up to 87% and 87% respectively). Following fesoterodine and

  10. Quetiapine extended release versus aripiprazole in children and adolescents with first-episode psychosis: the multicentre, double-blind, randomised tolerability and efficacy of antipsychotics (TEA) trial

    DEFF Research Database (Denmark)

    Pagsberg, Anne Katrine; Jeppesen, Pia; Klauber, Dea Gowers

    2017-01-01

    of quetiapine-extended release (quetiapine-ER) versus aripiprazole in children and adolescents with first-episode psychosis, to determine whether differences between the two treatments were sufficient to guide clinicians in their choice of one drug over the other. Methods In this multicentre, double......-blind, randomised trial in seven Danish university clinics, we recruited children and adolescents aged 12–17 years with a diagnosis of ICD-10 schizophrenia-spectrum disorder, delusional disorder, or affective-spectrum psychotic disorder, and psychotic symptoms scoring at least 4 on at least one of the following......-generated concealed sequence with a block size of 8, and stratified by baseline PANSS positive score (≤20 points or >20 points) and age (12–14 years or 15–17 years). Study drugs were administered in identical capsules, and interventions, assessments, and data analysis were done masked. The primary outcome was PANSS...

  11. Clinical recommendation on paliperidone extended-release tablet in schizophrenia therapy%帕利哌酮缓释片临床用药指导意见

    Institute of Scientific and Technical Information of China (English)

    舒良; 蔡焯基; 吉中孚; 江开达; 司天梅; 张鸿燕; 梅其一; 贾福军; 陆峥

    2011-01-01

    精神分裂症是一组病因未明的精神疾病,其病程迁延,易慢性化,多数患者会出现精神残疾.目前的治疗目标不仅是控制症状,还要改善患者的社会功能.文中综述了帕利哌酮缓释片的药理特点,并就其临床使用提出指导意见.帕利哌酮缓释片是一种新型第二代抗精神病药,其有效成分帕利哌酮是利培酮的活性代谢产物,同时OROS控释技术可以带来平稳的血药浓度.帕利哌酮缓释片起效迅速,能够全面有效控制症状,安全性良好,同时可以显著改善患者的社会功能.%Schizophrenia is a group of disabling disorders with uncertain cause. Its course can be presented as one episode or span into a chronic state, ultimately requiring lifelong treatment. The treatment goals of schizophrenia are to rapidly control symptoms, and to gain a result of improved personal and social functioning. In this paper, clinical recommendation on paliperidone extended-release (ER) tablet in schizophrenia therapy was reviewed. Paliperidone ER is a recently developed atypical antipsychotic drug available for the treatment of schizo-phrenia. Paliperidone (9-hydroxy risperidone) is the major active metabolite of risperidone. By the unique extended-release delivery system, paliperidone ER can steadily deliver paliperidone and maintain steady plasma concentrations. It is efficacious in improving symptoms and social functioning of schizophrenia patients, and is well tolerated.

  12. Candidate metrics for evaluating the impact of prescriber education on the safe use of extended-release/long-acting (ER/LA) opioid analgesics.

    Science.gov (United States)

    Willy, Mary E; Graham, David J; Racoosin, Judith A; Gill, Rajdeep; Kropp, Garner F; Young, Jessica; Yang, Jeff; Choi, Joyce; MaCurdy, Thomas E; Worrall, Chris; Kelman, Jeffrey A

    2014-09-01

    The objective of this study was to develop metrics to assess opioid prescribing behavior as part of the evaluation of the Extended-Release/Long-Acting (ER/LA) Opioid Analgesic Risk Evaluation and Mitigation Strategies (REMS). Candidate metrics were selected using published guidelines, examined using sensitivity analyses, and applied to cross-sectional rolling cohorts of Medicare patients prescribed with extended-release oxycodone (ERO) between July 2, 2006 and July 1, 2011. Potential metrics included prescribing opioid-tolerant-only ER/LA opioid analgesics to non-opioid-tolerant patients, prescribing early fills to patients, and ordering drug screens. Proposed definitions for opioid tolerance were seven continuous days of opioid usage of at least 30 mg oxycodone equivalents, within the 7 days (primary) or 30 days (secondary) prior to first opioid-tolerant-only ERO prescription. Forty-four percent of opioid-tolerant-only ERO episodes met the primary opioid tolerance definition; 56% met the secondary definition. Fills were deemed "early" if a prescription was filled before 70% (primary) or 50% (secondary) of the prior prescription's days' supply was to be consumed. Five percent (primary) and 2% (secondary) of episodes had more than or equal to two early fills during treatment. At least one drug screen was billed in 14% of episodes. Stratified analyses indicated that older patients were less likely to be opioid tolerant at the time of the first opioid-tolerant-only ERO prescription. Investigators propose three metrics to monitor changes in prescribing behaviors for opioid analgesics that might be used to evaluate the ER/LA Opioid Analgesics REMS. Low frequencies of patients, particularly those >85 years, were likely to be opioid tolerant prior to receiving prescriptions for opioid-tolerant-only ERO. Wiley Periodicals, Inc.

  13. Patient-reported outcomes to assess the efficacy of extended-release guaifenesin for the treatment of acute respiratory tract infection symptoms.

    Science.gov (United States)

    Albrecht, Helmut; Vernon, Margaret; Solomon, Gail

    2012-12-27

    Guaifenesin is a component of medicines used to improve symptoms associated with upper respiratory tract infections. Patient-reported outcome instruments are valuable for evaluating symptom improvements; however, a validated tool to assess efficacy of mucoactive drugs does not exist. We compared the efficacy of extended-release guaifenesin with placebo for treatment of symptoms of upper respiratory tract infection using subjective efficacy assessments in a pilot study and confirmed precision of assessments in a validation study. The pilot study was a randomized, double-blind study where patients were dosed with either 1200 mg extended-release guaifenesin (n = 188) or placebo (n = 190), every 12 hours for 7 days. Efficacy was assessed using subjective measures including the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and the Wisconsin Upper Respiratory Symptom Survey. End-of-study assessments were completed by patients and investigator. The validation study consisted of two phases. In Phase I, subjects completed interviews to gather evidence to support the content validity of the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and Patient's End-of-Treatment Assessment. Phase II examined the psychometric properties of assessments evaluated in Phase I of the validation study using data from the pilot study. Subjective measures of efficacy at Day 4 showed the most prominent difference between treatment groups, in favor of guaifenesin. The 8-symptom related questions (SUM8) in the Daily Cough and Phlegm Diary, analyzed as a composite score appeared to be the strongest candidate endpoint for further evaluation. Results from the interviews in Phase I supported the content of the assessments which were validated during Phase II. Treatments were well tolerated. Results from the clinical pilot and validation studies showed that the SUM8 diary scores were robust and reliable for use as efficacy endpoints in studies of

  14. NEW STABILITY INDICATING RP-LC METHOD FOR SIMULTANEOUS QUANTIFICATION OF RELATED IMPURITIES OF LAMIVUDINE, TENOFOVIR DISOPEOXIL FUMARATE AND NEVIRAPINE IN EXTENDED RELEASE TABLET DOSAGE FORMS

    Directory of Open Access Journals (Sweden)

    Lanka A.Rama Prasad

    2012-11-01

    Full Text Available The objective of the current study was to develop and validate precise, specific and stability-indicating reverse phase LC method for the simultaneous quantitative determination of Lamivudine, Tenofovir disoproxil fumarate and Nevirapine and their related impurities. The determination was done for extended release tablets dosage form where Tenofovir and Lamivudine are formulated into immediate release and Nevirapine into extended relase. The pharmaceutical formulation along with individual active ingredients was subjected to stress conditions of hydrolysis (acid and base, oxidation and thermal degradation as per International Conference on Harmonization (ICH prescribed stress conditions to show the stability-indicating power of the method. It was found Tenofovir disoproxil fumarate is very sensitive to various stress conditions and readily degrades into Monoester impurity. The chromatographic conditions were optimized using an impurity-spiked solution and the samples generated from forced degradation studies. Regression analysis shows an r value (correlation coefficient of greater than 0.997 for individual active drug substances and their all the related impurities. The chromatographic separation was achieved on a core shell technology C18 stationary phase. The method employed a linear gradient elution and the detection wavlength was set at 260 nm. The mobile phases consists of buffer and acetonitrile delivered at a flow rate of 0.8 mL•min–1. The stress samples were assayed against a qualified reference standard and the mass balance was found to be close to 98.5%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.

  15. A randomized double-blind, placebo-controlled trial of venlafaxine-extended release for co-occurring cannabis dependence and depressive disorders.

    Science.gov (United States)

    Levin, Frances R; Mariani, John; Brooks, Daniel J; Pavlicova, Martina; Nunes, Edward V; Agosti, Vito; Bisaga, Adam; Sullivan, Maria A; Carpenter, Kenneth M

    2013-06-01

    To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. This was a randomized, 12-week, double-blind, placebo-controlled trial of out-patients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. The trial was conducted at two university research centers in the United States. One hundred and three cannabis-dependent adults participated in the trial. The primary outcome measures were (i) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and (ii) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. The proportion of patients achieving a clinically significant mood improvement (50% decrease in Hamilton Depression score from baseline) was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (χ1 (2)  = 0.48, P = 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (χ1 (2)  = 7.46, P depressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use. © 2013 Society for the Study of Addiction.

  16. Serum posaconazole levels among haematological cancer patients taking extended release tablets is affected by body weight and diarrhoea: single centre retrospective analysis.

    Science.gov (United States)

    Miceli, Marisa H; Perissinotti, Anthony J; Kauffman, Carol A; Couriel, Daniel R

    2015-07-01

    The posaconazole extended release tablet formulation was developed to improve bioavailability relative to the oral suspension. Therapeutic drug monitoring has been used to optimise posaconazole dosing to achieve a target trough level ≥0.7 μg ml(-1). We retrospectively evaluated 28 patients with haematological malignancies who received posaconazole tablets for antifungal prophylaxis. Posaconazole serum trough levels were obtained 5 days after initiation of therapy. Mean trough level was 1.19 ± 0.63 μg ml(-1), and 71% achieved a trough level ≥0.7 μg ml(-1). Diarrhoea was associated with lower mean trough levels (0.65 ± 0.08 μg ml(-1) vs. 1.31 ± 0.13 μg ml(-1)), P = 0.002. Mean trough levels were lower in patients ≥90 kg (0.74 ± 0.09 μg ml(-1)) vs. Posaconazole delayed release tablets attain appropriate trough levels in most patients, but patients with a higher weight and those experiencing diarrhoea are more likely to have lower levels.

  17. Pharmacokinetic Studies in Healthy Subjects for the Development of an Extended-Release Tablet Formulation of Guaifenesin: A 505(b)(2) New Drug Application Approval.

    Science.gov (United States)

    Vilson, Lineau; Owen, Joel S

    2013-01-01

    Guaifenesin is an expectorant used to improve mucociliary clearance (MCC) and relieve chest congestion from upper respiratory tract infections. Immediate-release (IR) guaifenesin requires dosing every 4 hours to maintain efficacy because of the drug's short half-life. Extended-release (ER) guaifenesin has been developed to prolong efficacy and reduce dosing frequency. As part of the 505(b)(2) new drug application (NDA), the pharmacokinetics (PK) of an ER bi-layer tablet formulation of guaifenesin (Mucinex®) and bioequivalence to an over-the-counter (OTC) monograph IR formulation were evaluated in healthy subjects. In one study, subjects received 1,200 mg ER guaifenesin every 12 hours or 400 mg IR guaifenesin every 4 hours for 6 days. Steady-state exposures were equivalent between the two products, as demonstrated by AUC and Cmax . In another study, subjects received a single dose of 600 mg (fasted) or 1,200 mg (fasted or fed) ER bi-layer tablet formulations. AUC and Cmax were equivalent between both states for the 1,200 mg ER dose. However, Tmax of 1,200 mg ER guaifenesin was later in the fed than the fasted state. ER guaifenesin is bioequivalent to corresponding OTC monograph doses of IR guaifenesin. ER guaifenesin offers a convenient 12-hour dosing alternative to 4-hour dosing of IR guaifenesin. © The Author(s) 2013.

  18. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation

    DEFF Research Database (Denmark)

    Franek, F; Jarlfors, A; Larsen, F.

    2015-01-01

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desve......Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step...... for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq®, an extended release formulation...... (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp®) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions...

  19. Changes in misuse and abuse of prescription opioids following implementation of Extended-Release and Long-Acting Opioid Analgesic Risk Evaluation and Mitigation Strategy.

    Science.gov (United States)

    Bucher Bartelson, Becki; Le Lait, M Claire; Green, Jody L; Cepeda, M Soledad; Coplan, Paul M; Maziere, Jean-Yves; Wedin, Gregory P; Dart, Richard C

    2017-07-31

    An unintended consequence of extended-release (ER) and long-acting (LA) prescription opioids is that these formulations can be more attractive to abusers than immediate-release (IR) formulations. The US Food and Drug Administration recognized these risks and approved the ER/LA Opioid Analgesic Risk Evaluation and Mitigation Strategy (ER/LA REMS), which has a goal of reducing opioid misuse and abuse and their associated consequences. The primary objective of this analysis is to determine whether ER/LA REMS implementation was associated with decreased reports of misuse and abuse. Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS(R)) System Poison Center Program were utilized. Poison center cases are assigned a reason for exposure, a medical outcome, and a level of health care received. Rates adjusted for population and drug utilization were analyzed over time. RADARS System Poison Center Program data indicate a notable decrease in ER/LA opioid rates of intentional abuse and misuse as well as major medical outcomes or hospitalizations following implementation of the ER/LA REMS. While similar decreases were observed for the IR prescription opioid group, the decreasing rate for the ER/LA opioids exceeded the decreasing rates for the IR prescription opioids and was distinctly different than that for the prescription stimulants, indicating that the ER/LA REMS program may have had an additional effect on decreases in opioid abuse and intentional misuse beyond secular trends. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Potentiation of nerve growth factor-induced neurite outgrowth by fluvoxamine: role of sigma-1 receptors, IP3 receptors and cellular signaling pathways.

    Directory of Open Access Journals (Sweden)

    Tomoko Nishimura

    Full Text Available BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs have been widely used and are a major therapeutic advance in psychopharmacology. However, their pharmacology is quite heterogeneous. The SSRI fluvoxamine, with sigma-1 receptor agonism, is shown to potentiate nerve-growth factor (NGF-induced neurite outgrowth in PC 12 cells. However, the precise cellular and molecular mechanisms underlying potentiation by fluvoxamine are not fully understood. In this study, we examined the roles of cellular signaling pathways in the potentiation of NGF-induced neurite outgrowth by fluvoxamine and sigma-1 receptor agonists. METHODS AND FINDINGS: The effects of three SSRIs (fluvoxamine, sertraline, paroxetine and three sigma-1 receptor agonists (SA4503, 4-phenyl-1-(4-phenylbutyl piperidine (PPBP, and dehydroepiandrosterone (DHEA-sulfate on NGF-induced neurite outgrowth in PC12 cells were examined. Also examined were the effects of the sigma-1 receptor antagonist NE-100, inositol 1,4,5-triphosphate (IP(3 receptor antagonist, and specific inhibitors of signaling pathways in the potentiation of NGF-induced neurite outgrowth by selective sigma-1 receptor agonist SA4503. Fluvoxamine (but not sertraline or paroxetine and the sigma-1 receptor agonists SA4503, PPBP, and DHEA-sulfate significantly potentiated NGF-induced neurite outgrowth in PC12 cells in a concentration-dependent manner. The potentiation by fluvoxamine and the three sigma-1 receptor agonists was blocked by co-administration of the selective sigma-1 receptor antagonist NE-100, suggesting that sigma-1 receptors play a role in blocking the enhancement of NGF-induced neurite outgrowth. Moreover, the potentiation by SA4503 was blocked by co-administration of the IP(3 receptor antagonist xestospongin C. In addition, the specific inhibitors of phospholipase C (PLC-gamma, phosphatidylinositol 3-kinase (PI3K, p38MAPK, c-Jun N-terminal kinase (JNK, and the Ras/Raf/mitogen-activated protein kinase (MAPK

  1. Abuse Potential with Oral Route of Administration of a Hydrocodone Extended-Release Tablet Formulated with Abuse-Deterrence Technology in Nondependent, Recreational Opioid Users

    Science.gov (United States)

    Darwish, Mona; Ma, Yuju; Tracewell, William; Robertson, Philmore; Webster, Lynn R.

    2017-01-01

    Objective. To compare the oral abuse potential of hydrocodone extended-release (ER) tablet developed with CIMA® Abuse-Deterrence Technology with that of hydrocodone immediate release (IR). Design. Randomized, double-blind, placebo-controlled, crossover study. Setting and Patients. One study site in the United States; adult nondependent, recreational opioid users. Methods. After confirming their ability to tolerate and discriminate hydrocodone IR 45 mg from placebo, eligible participants were randomized to receive each of the following oral treatments once: finely crushed placebo, hydrocodone IR 45-mg powder, intact hydrocodone ER 45-mg tablet, and finely crushed hydrocodone ER 45-mg tablet. Primary pharmacodynamic measure was “at the moment” drug liking. Secondary measures included overall drug liking, drug effects (e.g., balance, positive, negative, sedative), pupillometry, pharmacokinetics, and safety. Results. Mean maximum effect (Emax) for “at the moment” drug liking was significantly lower for intact (53.9) and finely crushed hydrocodone ER (66.9) vs. hydrocodone IR (85.2; P < 0.001). Drug liking for intact hydrocodone ER was comparable to placebo (Emax: 53.9 vs. 53.2). Secondary measures were consistent with these results, indicating that positive, negative, and sedative drug effects were diminished with intact and crushed hydrocodone ER tablet vs. hydrocodone IR. The 72-hour plasma concentration-time profile for each treatment mimicked its respective “at the moment” drug-liking-over-time profile. Incidence of adverse events was lower with intact hydrocodone ER (53%) vs. hydrocodone IR (79%) and finely crushed hydrocodone ER (73%). Conclusions. The oral abuse potential of hydrocodone ER (intact and finely crushed) was significantly lower than hydrocodone IR in healthy, nondependent, recreational opioid users. Hydrocodone ER was generally well tolerated. PMID:27330154

  2. Success rate, efficacy, and safety/tolerability of overnight switching from immediate- to extended-release pramipexole in advanced Parkinson's disease.

    Science.gov (United States)

    Schapira, A H V; Barone, P; Hauser, R A; Mizuno, Y; Rascol, O; Busse, M; Debieuvre, C; Fraessdorf, M; Poewe, W

    2013-01-01

    For Parkinson's disease (PD), an extended-release (ER) pramipexole formulation taken once daily, has shown efficacy, safety, and tolerability resembling those of immediate-release (IR) pramipexole taken three times daily. The present study assessed, in advanced PD, the success of an overnight switch from adjunctive IR to ER. Levodopa users experiencing motor fluctuations were randomized to adjunctive double-blind (DB) placebo, IR, or ER. Amongst completers of ≥18 weeks, ER recipients were kept on DB ER, whilst IR recipients were switched overnight to DB ER at unchanged daily dosage. After a DB week, switch success was assessed. During the next 5 weeks, all patients underwent ER titration to optimal open-label maintenance dosage. One week post-switch, 86.2% of 123 IR-to-ER and 83.8% of 105 ER-to-ER patients had ≤15% (or ≤3-point, for pre-switch scores ≤20) increase on UPDRS Parts II + III, and 77.9% (of 122) and 70.2% (of 104) had ≤1-h increase in daily OFF-time. At 32 weeks, the groups showed comparable improvements from DB baseline (pramipexole inception), including, on UPDRS II + III, adjusted mean (SE) changes of -14.8 (1.5) for IR-to-ER and -13.3 (1.6) for ER-to-ER. Rates of premature discontinuation owing to adverse events were 6.5% for IR-to-ER and 4.9% for ER-to-ER. By OFF-time and UPDRS criteria, majorities of patients with advanced PD were successfully switched overnight from pramipexole IR to ER at unchanged daily dosage. During subsequent maintenance, pramipexole showed sustained efficacy, safety, and tolerability, regardless of formulation (IR or ER) in the preceding DB trial. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

  3. Antiplatelet Effect Durability of a Novel, 24-Hour, Extended-Release Prescription Formulation of Acetylsalicylic Acid in Patients With Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Gurbel, Paul A; Bliden, Kevin P; Chaudhary, Rahul; Patrick, Jeff; Liu, Fang; Chen, Gailing; McLeod, Christopher; Tantry, Udaya S

    2016-12-15

    High platelet reactivity and high platelet turnover have been implicated in incomplete platelet inhibition during immediate-release acetylsalicylic acid therapy in patients with type 2 diabetes mellitus (DM). An extended-release acetylsalicylic acid (ER-ASA; Durlaza) formulation was developed to provide 24-hour antithrombotic effects with once-daily dosing. The objective of the study was to evaluate the antiplatelet effects of ER-ASA in patients with DM. In this open-label, single-center study, patients with DM (n = 40) and multiple cardiovascular risk factors received ER-ASA 162.5 mg/day for 14 ± 4 days. Multiple platelet function tests, serum and urinary thromboxane B2 metabolites, prostacyclin metabolite, and high-sensitive C-reactive protein levels were assessed at 1, 12, 16, and 24 hours post-dose. Patients with high platelet turnover and/or high platelet reactivity were treated with ER-ASA 325 mg/day for 14 ± 4 days, and laboratory analyses were repeated. All patients responded to ER-ASA 162.5 mg/day as measured by arachidonic acid-induced aggregation, and there was no loss of the platelet inhibitory effect of ER-ASA 162.5 mg/day over 24 hours post-dose (p = not significant). The antiplatelet effect was sustained over 24 hours for all platelet function measurements. Mean 1- to 24-hour serum thromboxane B2 levels were low with both doses and were lower with ER-ASA 325 mg/day compared with 162.5 mg/day therapy (p = 0.002). In conclusion, ER-ASA 162.5 mg daily dose provided sustained antiplatelet effects over 24 hours in patients with type 2 DM and multiple cardiovascular risk factors and had a favorable tolerability profile.

  4. A randomized, double-blind study of 30 versus 20 mg dexmethylphenidate extended-release in children with attention-deficit/hyperactivity disorder: late-day symptom control.

    Science.gov (United States)

    Brams, Matthew; Turnbow, John; Pestreich, Linda; Giblin, John; Childress, Ann; McCague, Kevin; Muniz, Rafael

    2012-10-01

    The objective of this study was to evaluate the safety and efficacy of dexmethylphenidate extended-release (d-MPH-ER) 30 versus 20 mg in children with attention-deficit/hyperactivity disorder (ADHD) in a 12-hour laboratory classroom setting. In a randomized, double-blind, 3-period × 3-treatment, crossover study, children aged 6 to 12 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-diagnosed ADHD previously stabilized on MPH (40-60 mg/d) or D-MPH (20-30 mg/day) [corrected] were randomized to receive D-MPH-ER 20 mg/day, 30 mg/day, [corrected] or placebo for 7 days each. Primary efficacy measurements were change in the average SKAMP-Combined [corrected] score from predose to 10, 11, and 12 hours postdose [Avg(10-12)] between 30 mg [corrected] and 20 mg D-MPH-ER. Safety was assessed by adverse events, (AEs), [corrected] vital sign monitoring, and ECGs. [corrected] A total of 165 children were randomized, and 162 included in the intent-to-treat analysis. Mean Avg (10-12) change from pre-dose [corrected] in SKAMP-Combined score was significantly greater for D-MPH-ER 30 mg (-4.47) compared with D-MPH-ER 20 mg (-2.02; P = 0.002). Most common adverse events (≥ 3% in any group) were decreased appetite (6.1%, 4.9%, and 0%), headache (4.3%, 4.3%, and 1.9%), abdominal pain (3.7%, 3.1%, and 3.1%), and tachycardia (1.2%, 3.1%, and 0.6%) for D-MPH-ER 30 mg, D-MPH-ER 20 mg, and placebo, respectively). Significantly greater improvement in ADHD symptoms was noted with D-MPH-ER 30 mg compared with D-MPH-ER 20 mg at hours 10 through 12. Tolerability was comparable between doses. Dexmethylphenidate extended-release 30-mg dose may provide further benefit to patients who do not maintain optimal symptom control later in the day with D-MPH-ER 20 mg.

  5. Relationship between glycemic status and progression of carotid intima-media thickness during treatment with combined statin and extended-release niacin in ARBITER 2

    Directory of Open Access Journals (Sweden)

    Allen J Taylor

    2007-03-01

    Full Text Available Allen J Taylor, Daming Zhu, Lance E Sullenberger, Hyun J Lee, Jeannie K Lee, Karen A Grace Cardiology Service, Walter Reed Army Medical Center, Washington, DC, USA Background: We previously reported in a placebo-controlled study that extended-release niacin slowed the progression of carotid atherosclerosis when added to statin monotherapy. This analysis examines the relationship between glycemic status and the effects of niacin on common carotid intima-media thickness (CIMT and HDL cholesterol.Methods: Post-hoc, subgroup analysis of ARBITER 2, a randomized, placebo-controlled trial of once-daily extended-release niacin (1000 mg added to background statin therapy in 167 patients (mean age 67 years with known coronary heart disease. The primary analysis was a comparison of the primary endpoint, the change in CIMT, between participants with either normal glycemic status, diabetes mellitus (DM or the metabolic syndrome (MS.Results: Baseline cardiovascular risk variables were significantly worse in those with abnormal glycemic status, particularly among subjects with MS. Niacin increased HDL-C to a similar degree (~20% across normals, DM and MS. Placebo-treated patients had the greatest CIMT progression, regardless of glycemic status. The lowest progression rate was observed in niacin treated patients with normal glycemic status. Among all niacin treated subjects, there was a significant linear relationship between change in CIMT and change in HDL-C (r = –0.16; p = 0.05, which was of similar magnitude in subgroups with normal glycemic status (r = –0.23; p = 0.08 and DM (r = –0.22; p = 0.17. In those with MS, there was no relationship between changes in HDL and CIMT, (r = 0.11; p = 0.44, whereas blood glucose was positive correlated to change in CIMT (r = 0.30; p = 0.04. In multivariable linear models controlling for MS characteristics and blood glucose changes, only the change in HDL independently predicted change in CIMT.Conclusions: During

  6. Patient-reported outcomes to assess the efficacy of extended-release guaifenesin for the treatment of acute respiratory tract infection symptoms

    Directory of Open Access Journals (Sweden)

    Albrecht Helmut

    2012-12-01

    Full Text Available Abstract Background Guaifenesin is a component of medicines used to improve symptoms associated with upper respiratory tract infections. Patient-reported outcome instruments are valuable for evaluating symptom improvements; however, a validated tool to assess efficacy of mucoactive drugs does not exist. We compared the efficacy of extended-release guaifenesin with placebo for treatment of symptoms of upper respiratory tract infection using subjective efficacy assessments in a pilot study and confirmed precision of assessments in a validation study. Methods The pilot study was a randomized, double-blind study where patients were dosed with either 1200 mg extended-release guaifenesin (n = 188 or placebo (n = 190, every 12 hours for 7 days. Efficacy was assessed using subjective measures including the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and the Wisconsin Upper Respiratory Symptom Survey. End-of-study assessments were completed by patients and investigator. The validation study consisted of two phases. In Phase I, subjects completed interviews to gather evidence to support the content validity of the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and Patient’s End-of-Treatment Assessment. Phase II examined the psychometric properties of assessments evaluated in Phase I of the validation study using data from the pilot study. Results Subjective measures of efficacy at Day 4 showed the most prominent difference between treatment groups, in favor of guaifenesin. The 8-symptom related questions (SUM8 in the Daily Cough and Phlegm Diary, analyzed as a composite score appeared to be the strongest candidate endpoint for further evaluation. Results from the interviews in Phase I supported the content of the assessments which were validated during Phase II. Treatments were well tolerated. Conclusions Results from the clinical pilot and validation studies showed that the SUM8 diary

  7. Efficacy and safety of a once-daily extended-release formulation of pramipexole switched from an immediate-release formulation in patients with advanced Parkinson's disease: results from an open-label study.

    Science.gov (United States)

    Takanashi, M; Shimo, Y; Hatano, T; Oyama, G; Hattori, N

    2013-12-01

    This study aimed to evaluate the efficacy and safety of an extended-release tablet formulation of pramipexole (PPX-ER) given once daily when switched from an immediate-release tablet formulation (PPX-IR) given 3 times daily. This open-label study included 29 patients with idiopathic Parkinson's disease (PD) who were followed for 8 weeks. Primary endpoints were Unified Parkinson's Disease Rating Scale (UPDRS) part III score, a physician evaluation of motor symptoms; nocturnal and early morning symptoms (NEMS) score, based on the results for 4 items in the Parkinson's Disease Sleep Scale and the Movement Disorder Society - sponsored revision of the UPDRS; and patients' formulation preference, determined through questionnaires. Secondary endpoints were nocturnal sleep disturbance, evaluated using the revised version of the Parkinson's Disease Sleep Scale (PDSS-2); quality of life, evaluated using the 39-item Parkinson's Disease Questionnaire (PDQ-39); Clinical Global Impression-Improvement (CGI-I) score; Patient Global Impression-Improvement (PGI-I) score; and caregiver formulation preference. UPDRS part III score (mean ± SD) was significantly decreased after 4 weeks (13.9 ± 7.3; P=0.030) and 8 weeks (12.2 ± 7.3; P<0.001) from baseline (15.3 ± 7.0). However, no significant change was found in NEMS scale, PDSS-2 or PDQ-39 scores. After 8 weeks, the responder rates based on CGI-I and PGI-I scores were 27.6% and 20.7%, respectively. As a result of the questionnaire, 63.0% of patients and 58.8% of their caregivers preferred PPX-ER. A non-serious drug-related adverse event (diarrhea) was observed in one patient. In conclusion, PPX-ER can be considered as a useful treatment option when PPX-IR needs to be switched to other dopamine agonists.This study is registered with UMIN-CTR (UMIN000006521).

  8. One-year results with extended-release tacrolimus/MMF, tacrolimus/MMF and cyclosporine/MMF in de novo kidney transplant recipients.

    Science.gov (United States)

    Silva, H T; Yang, H C; Abouljoud, M; Kuo, P C; Wisemandle, K; Bhattacharya, P; Dhadda, S; Holman, J; Fitzsimmons, W; First, M Roy

    2007-03-01

    Once-daily tacrolimus extended-release formulation (Prograf XL, formerly referred to as MR or MR4) was compared with the twice-a-day tacrolimus formulation (TAC) and cyclosporine microemulsion (CsA), all administered in combination with mycophenolate mofetil (MMF), corticosteroids and basiliximab induction, in a phase 3, randomized (1:1:1), open-label trial in 638 de novo kidney transplant recipients. In combination with MMF and corticosteroids, XL had an efficacy profile comparable to TAC and CsA. XL/MMF and TAC/MMF were statistically noninferior at 1-year posttransplantation to CsA/MMF for the primary efficacy endpoint, efficacy failure (death, graft loss, biopsy-confirmed acute rejection (BCAR) or lost to follow-up). One-year patient and graft survival were 98.6% and 96.7% in the XL/MMF group, 95.7% and 92.9% in TAC/MMF group and 97.6% and 95.7% in CsA/MMF group. The safety profile of XL in comparison with CsA was similar to that observed with TAC in this study and consistent with previously published reports of TAC in comparison with CsA. The results support the safety and efficacy of tacrolimus in combination with MMF, corticosteroids and basiliximab induction, as well as XL as a safe and effective once-daily dosing alternative.

  9. Effect of Extended-Release Niacin on New-Onset Diabetes Among Hyperlipidemic Patients Treated With Ezetimibe/Simvastatin in a Randomized Controlled Trial

    Science.gov (United States)

    Guyton, John R.; Fazio, Sergio; Adewale, Adeniyi J.; Jensen, Erin; Tomassini, Joanne E.; Shah, Arvind; Tershakovec, Andrew M.

    2012-01-01

    OBJECTIVE To determine the effect of niacin on fasting glucose (FG) and new-onset diabetes in statin/ezetimibe-treated patients. RESEARCH DESIGN AND METHODS This was a prespecified secondary analysis among 942 hyperlipidemic patients randomized to ezetimibe/simvastatin (E/S; 10/20 mg) or E/S + extended-release niacin (N; titrated to 2 g) over 64 weeks. RESULTS FG levels peaked by 8–12 weeks, then declined even without antidiabetic medication. At 64 weeks, 3.5% taking E/S+N versus 2.6% taking E/S met criteria for new-onset diabetes (P = 0.66). An additional 1.4% taking E/S+N versus 0.4% taking E/S transiently met criteria for diabetes and then remitted (P = 0.46). Of 28 new-diabetes diagnoses in the E/S+N group, 25 occurred by 24 weeks. Among patients with baseline diabetes, 13.9% taking E/S+N and 11.6% taking E/S underwent antidiabetic treatment modification. CONCLUSIONS Increased FG and new-onset diabetes with E/S+N occurred mainly around the time of initial uptitration of N and often improved or remitted without specific treatment. PMID:22338103

  10. Phentermine and topiramate extended-release: a new treatment for obesity and its role in a complications-centric approach to obesity medical management.

    Science.gov (United States)

    Garvey, William Timothy

    2013-09-01

    Weight-management options include lifestyle modifications, bariatric surgery and, until recently, limited pharmacotherapy. Phentermine and topiramate extended-release (phentermine/topiramate ER) has recently been approved in the USA for chronic weight management in obese adults and overweight adults with weight-related co-morbidities in conjunction with a reduced-calorie diet and increased physical activity. This review describes the pharmacology and clinical trials data for phentermine/topiramate ER and its role in a complications-centric approach to medical care of the overweight and obese patient. Phentermine/topiramate ER is an effective and safe weight-loss medication that can produce and sustain approximately 10% loss of body weight. This is a landmark development in the pharmacotherapy of obesity. By offering an effective medical option to complement lifestyle and surgical approaches, phentermine/topiramate ER enables a comprehensive medical model for obesity care. The overall approach to the overweight and obese patient should be to identify individuals who will benefit most from therapy based on cardiometabolic or mechanical complications, establish therapeutic targets and goals for ameliorating these complications and selecting the treatment modality and intensity for weight loss to achieve these goals. This complications-centric model emphasizes weight loss as a tool to ameliorate obesity-related complications and optimizes benefit/risk for achieving the best outcomes in overweight/obese patients.

  11. Caffeine-mediated inhibition of calcium release channel inositol 1,4,5-trisphosphate receptor subtype 3 blocks glioblastoma invasion and extends survival.

    Science.gov (United States)

    Kang, Sang Soo; Han, Kyung-Seok; Ku, Bo Mi; Lee, Yeon Kyung; Hong, Jinpyo; Shin, Hye Young; Almonte, Antoine G; Woo, Dong Ho; Brat, Daniel J; Hwang, Eun Mi; Yoo, Seung Hyun; Chung, Chun Kee; Park, Sung-Hye; Paek, Sun Ha; Roh, Eun Joo; Lee, Sung Joong; Park, Jae-Yong; Traynelis, Stephen F; Lee, C Justin

    2010-02-01

    Calcium signaling is important in many signaling processes in cancer cell proliferation and motility including in deadly glioblastomas of the brain that aggressively invade neighboring tissue. We hypothesized that disturbing Ca(2+) signaling pathways might decrease the invasive behavior of giloblastoma, extending survival. Evaluating a panel of small-molecule modulators of Ca(2+) signaling, we identified caffeine as an inhibitor of glioblastoma cell motility. Caffeine, which is known to activate ryanodine receptors, paradoxically inhibits Ca(2+) increase by inositol 1,4,5-trisphospate receptor subtype 3 (IP(3)R3), the expression of which is increased in glioblastoma cells. Consequently, by inhibiting IP(3)R3-mediated Ca(2+) release, caffeine inhibited migration of glioblastoma cells in various in vitro assays. Consistent with these effects, caffeine greatly increased mean survival in a mouse xenograft model of glioblastoma. These findings suggest IP(3)R3 as a novel therapeutic target and identify caffeine as a possible adjunct therapy to slow invasive growth of glioblastoma.

  12. Lower urinary tract symptoms associated with benign prostatic hyperplasia: combined treatment with fesoterodine fumarate extended-release and tamsulosin--a prospective study.

    Science.gov (United States)

    Konstantinidis, Charalampos; Samarinas, Michael; Andreadakis, Sotirios; Xanthis, Stylianos; Skriapas, Konstantinos

    2013-01-01

    To evaluate the efficacy and safety of fesoterodine extended-release (ER) plus tamsulosin in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Men aged ≥50 years, with LUTS, prostate volume ≤60 ml and International Prostate Symptom Score (IPSS) ≥13 were enrolled in this study. 173 consecutive patients were treated initially with tamsulosin (0.4 mg) for 1 week. At the second visit, 47 patients out of the sample of 173 who were still experiencing inconvenient LUTS were randomized into two groups. The first group received a therapy with tamsulosin and fesoterodine combination (group 1, n = 24) while the second continued the therapy with the single administration of tamsulosin (group 2, n = 23) for an additional 4-week period. There was no statistically significant difference in age, prostate volume, Q, and postvoid residual urine between the two groups. A statistical significance appeared in the combination group regarding the storage and the total IPSS values among the second and third visits (10.5 ± 1.4 to 8.5 ± 1.3 and 16.1 ± 1.8 to 13.7 ± 1.5 respectively). Regarding bothersome LUTS and storage symptoms, fesoterodine ER and tamsulosin combination was significantly more effective than the single administration of tamsulosin. Copyright © 2012 S. Karger AG, Basel.

  13. Dose-Response Analysis of the Effect of Carbidopa-Levodopa Extended-Release Capsules (IPX066) in Levodopa-Naive Patients With Parkinson Disease.

    Science.gov (United States)

    Mao, Zhongping Lily; Modi, Nishit B

    2016-08-01

    Parkinson disease is an age-related disorder of the central nervous system principally due to loss of dopamine-producing cells in the midbrain. Levodopa, in combination with carbidopa, is widely regarded as an effective treatment for the symptoms of Parkinson disease. A dose-response relationship is established for carbidopa-levodopa extended-release capsules (IPX066) in levodopa-naive Parkinson disease patients using a disease progression model. Unified Parkinson Disease Rating Scale (UPDRS) part II plus part III scores from 171 North American patients treated with placebo or IPX066 for approximately 30 weeks from a double-blind, parallel-group, dose-ranging study were used to develop the pharmacodynamic model. The model comprised 3 components: a linear function describing disease progression, a component describing placebo (or nonlevodopa) effects, and a component to describe the effect of levodopa. Natural disease progression in early Parkinson disease as measured by UPDRS was 11.6 units/year and faster in patients with more severe disease (Hoehn-Yahr stage 3). Maximum placebo/nonlevodopa response was 23.0% of baseline UPDRS. Maximum levodopa effect from IPX066 was 76.7% of baseline UPDRS, and the ED50 was 450 mg levodopa. Equilibration half-life for the effect compartment was 62.8 days. Increasing age increased and being female decreased equilibration half-life. The quantitative model allowed description of the entire time course of response to clinical trial intervention.

  14. The extended-release formulation of quetiapine fumarate (quetiapine XR) adjunctive treatment in partially responsive generalized anxiety disorder (GAD): An open label naturalistic study.

    Science.gov (United States)

    Gabriel, A

    2011-01-01

    To assess the effect of adjunctive treatment with extended-release formulation of quetiapine fumarate (quetiapine XR) to other antidepressants in the treatment of partially responsive, poorly functioning patients with generalized anxiety disorder was assessed. Twenty four consenting adult outpatients with confirmed DSM-IV diagnosis of generalized disorder were identified. All patients failed at least one 8-week treatment trial with SSRI or SNRI antidepressant. All were treated with quetiapine XR as an add on treatment to citalopram or vanlafaxine antidepressant for at least 12 weeks. The primary efficacy measure was the Clinical Global Impression Scale (CGI-S). Other scales included; the Hamilton Anxiety Scale (HAM-A) scale, Sheehan Disability Scale, and the Abnormal Involuntary Movement Scale (AIMS). Baseline measures prior to adding quetiapine XR were compared to those at 4, 8 and 12 weeks with the adjunctive treatment. Twenty three patients completed the trial. There was significant rapid resolution of the anxiety symptoms in all effectiveness measures, including the symptoms of anxiety as shown by changes from baseline in HAM-A, and CGI at four weeks. Improvement was maintained to week twelve. Impairments in work, social, and home responsibilities were also reduced significantly, and there were no significant changes in weight at 12 weeks. Patients tolerated the adjunctive treatment well. Quetiapine XR may have anxiolytic properties and could be used effectively as adjunctive treatment with SSRIs in GAD patients with partial response to SSRs or SNRISs. However double blind randomized trials are needed to support these results.

  15. Effects of once-daily extended release quetiapine fumarate (quetiapine XR) on quality of life and sleep in elderly patients with major depressive disorder.

    Science.gov (United States)

    Locklear, Julie C; Svedsäter, Henrik; Datto, Catherine; Endicott, Jean

    2013-07-01

    Major depressive disorder (MDD) is frequently associated with reduced quality of life (QoL) and sleep disturbance. We investigated the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy on QoL and sleep in elderly patients with MDD. Prospectively planned analysis of patient-reported data from an 11-week (9-week randomized; 2-week post-treatment), double-blind, placebo-controlled, Phase III study. Elderly patients (≥66 years; DSM-IV MDD; Hamilton Rating Scale for Depression [HAM-D] total score ≥22, HAM-D Item 1 score ≥2) were randomized to quetiapine XR (flexible dosing 50-300 mg/day) or placebo. MADRS total score change from randomization at Week 9. Patient-reported outcomes: Quality of Life, Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) % of maximum total score (Items 1-14), Q-LES-Q-SF Item 15 ('satisfaction with medication'), Q-LES-Q-SF Item 16 ('overall life satisfaction'), and Pittsburgh Sleep Quality Index (PSQI) global score. In total, 338 patients were randomized (166 quetiapine XR; 172 placebo). At Week 9, quetiapine XR significantly reduced MADRS total score (-16.33; difference: -7.54; 95% CI: -9.23, -5.85; pelderly patients with MDD. Copyright © 2013. Published by Elsevier B.V.

  16. Add-on-Statin Extended Release Nicotinic Acid/Laropiprant but Not the Switch to High-Dose Rosuvastatin Lowers Blood Pressure: An Open-Label Randomized Study

    Directory of Open Access Journals (Sweden)

    Anastazia Kei

    2011-01-01

    Full Text Available Introduction. Nicotinic acid (NA and statins have been associated with reductions in blood pressure (BP. Patients and Methods. We recruited 68 normotensive and hypertensive dyslipidemic patients who were treated with a conventional statin dose and had not achieved lipid targets. Patients were randomized to switch to high-dose rosuvastatin (40 mg/day or to add-on current statin treatment with extended release (ER NA/laropiprant (1000/20 mg/day for the first 4 weeks followed by 2000/40 mg/day for the next 8 weeks for 3 months. Results. Switching to rosuvastatin 40 mg/day was not associated with significant BP alterations. In contrast, the addition of ER-NA/laropiprant to current statin treatment resulted in a 7% reduction of systolic BP (from 134±12 to 125±10 mmHg, <.001 versus baseline and =.01 versus rosuvastatin group and a 5% reduction of diastolic BP (from 81±9 to 77±6 mmHg, =.009 versus baseline and =.01 versus rosuvastatin group. These reductions were significant only in the subgroup of hypertensives and were independent of the hypolipidemic effects of ER-NA/laropiprant. Conclusions. Contrary to the switch to high-dose rosuvastatin, the addition of ER-NA/laropiprant to statin treatment was associated with significant reductions in both systolic and diastolic BP.

  17. Long-term tolerability of tolterodine extended release in children 5-11 years of age: results from a 12-month, open-label study

    DEFF Research Database (Denmark)

    Nijman, Rien J M; Borgstein, Niels G; Ellsworth, Pamela

    2007-01-01

    suggestive of detrusor overactivity (>/=1 diurnal incontinence episode per 24h for >/=5 of 7 d) and >/=6 voids per 24h at baseline and had completed the 12-wk double-blind study. Patients received tolterodine ER (2mg once daily) for 12 mo. The primary end points were the incidence and severity of adverse......OBJECTIVE: To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). METHODS: This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI......-blind tolterodine ER, n=221; placebo, n=97). The majority of patients were white (90%), mean+/-SD age was 7.6+/-1.5 yr, and 54% were boys. Forty-nine percent of patients reported >/=1 AE during the study, similar to that observed in the preceding 12-wk study (42%). The most frequent AEs were urinary tract infection...

  18. A randomized, double-blind study of the efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR monotherapy in patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Wang G

    2014-01-01

    Full Text Available Gang Wang,1 Alexander McIntyre,2 Willie R Earley,3 Shane R Raines,3 Hans Eriksson4 1Beijing Anding Hospital, Capital Medical University, Beijing, People's Republic of China; 2Department of Psychiatry, Penticton Regional Hospital, Penticton, BC, Canada; 3AstraZeneca Pharmaceuticals, Wilmington, DE, USA; 4AstraZeneca R&D, Södertälje, Sweden Objectives: To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR monotherapy in patients with major depressive disorder (MDD. Patients and methods: This was a 10-week (8-week active treatment/2-week post-treatment randomized, double-blind, placebo- and active-controlled study (D1448C00004. Patients received quetiapine XR 150 mg/day, escitalopram 10 mg/day, or placebo; patients with an inadequate response (<20% improvement in Montgomery–Åsberg Depression Rating Scale [MADRS] total score at week two received double-dose treatment. The primary end point was week eight change from randomization in MADRS total score. Secondary end points included MADRS response (≥50% improvement and remission (score ≤8; Hamilton Rating Scale for Depression total and item 1; Hamilton Rating Scale for Anxiety total, psychic, and somatic; Clinical Global Impressions – Severity of Illness total; Pittsburgh Sleep Quality Index (PSQI global; and Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form percentage maximum total scores. Tolerability was assessed throughout. Results: A total of 471 patients was randomized. No significant improvements in MADRS total score were observed at week eight (last observation carried forward with either active treatment (quetiapine XR, -17.21 [P=0.174]; escitalopram, -16.73 [P=0.346] versus placebo (-15.61. There were no significant differences in secondary end points versus placebo, with the exception of week-eight change in PSQI global score (quetiapine XR, -4.96 [P<0.01] versus placebo, -3.37. Mixed-model repeated

  19. Evaluation of blood pressure and heart rate in patients with hypertension who received tapentadol extended release for chronic pain: a post hoc, pooled data analysis.

    Science.gov (United States)

    Biondi, David M; Xiang, Jim; Etropolski, Mila; Moskovitz, Bruce

    2014-08-01

    Hypertension is one of the most common co-existing conditions in patients with chronic pain, and the potential effects of an analgesic on heart rate and blood pressure are of particular concern for patients with hypertension. The purpose of this analysis was to evaluate changes in blood pressure and heart rate with tapentadol extended release (ER) treatment in patients with hypertension. We performed a post hoc analysis of data pooled from three randomized, placebo- and active-controlled, phase III studies of tapentadol ER for managing chronic osteoarthritis knee (NCT00421928, NCT00486811) or low back (NCT00449176) pain (15-week, double-blind treatment period). Data were independently analyzed for patients with a listed medical history of hypertension at baseline and patients with at least one listed concomitant antihypertensive medication at baseline. Heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured at each visit. In patients with a listed medical history of hypertension (n = 1,464), least-squares mean (LSM [standard error (SE)]) changes from baseline to endpoint with placebo, tapentadol ER, and oxycodone HCl controlled release (CR), respectively, were -0.7 (0.44), 0.2 (0.43), and -0.9 (0.45) beats per minute (bpm) for heart rate; -2.4 (0.64), -2.7 (0.64), and -3.7 (0.67) mmHg for SBP; and -1.0 (0.39), -1.3 (0.39), and -2.3 (0.41) mmHg for DBP; in patients with at least one listed concomitant antihypertensive medication (n = 1,376), the LSM (SE) changes from baseline to endpoint were -0.6 (0.45), 0.1 (0.44), and -0.7 (0.47) bpm for heart rate; -1.8 (0.66), -3.3 (0.65), and -3.7 (0.69) mmHg for SBP; and -0.7 (0.40), -1.4 (0.40), and -2.3 (0.42) mmHg for DBP. No clinically meaningful mean changes in heart rate or blood pressure were observed for the evaluated cohorts of patients with hypertension who were treated with tapentadol ER (100-250 mg twice daily).

  20. Efficacy and Safety of Extended-Release Quetiapine Fumarate in Youth with Bipolar Depression: An 8 Week, Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Pathak, Sanjeev; Earley, Willie R; Liu, Sherry; DelBello, Melissa P

    2014-01-01

    Abstract Objective: Quetiapine is an atypical antipsychotic with demonstrated efficacy in the treatment of adolescent schizophrenia and pediatric bipolar mania. Large, placebo-controlled studies of interventions in pediatric bipolar depression are lacking. The current study investigated the efficacy and safety of quetiapine extended-release (XR) in patients 10–17 years of age, with acute bipolar depression. Methods: This multicenter, double-blind, randomized, placebo-controlled study investigated quetiapine XR (dose range, 150–300 mg/day) in pediatric outpatients with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar I or bipolar II disorder (current or most recent episode depressed) treated for up to 8 weeks (ClinicalTrials.gov identifier: NCT00811473). The primary study outcome was mean change in Children's Depression Rating Scale–Revised (CDRS-R) total score. Secondary efficacy outcomes included CDRS-R-based response and remission rates. Results: Of 193 patients randomized to treatment, 144 patients completed the study (75.3% of quetiapine XR group [n=70]; 74.0% of placebo group [n=74]). Least squares mean changes in CDRS-R total score at week 8 were: −29.6 (SE, 1.65) with quetiapine XR and −27.3 (SE, 1.60) with placebo, a between-treatment group difference of −2.29 (SE, 1.99; 95% CI, −6.22, 1.65; p=0.25; mixed-model for repeated measures analysis). Rates of response and remission did not differ significantly between treatment groups. The safety profile of quetiapine XR was broadly consistent with the profile reported previously in adult studies of quetiapine XR and pediatric studies of quetiapine immediate-release (IR). Potentially clinically significant elevations in clinical chemistry values included triglycerides (9.3%, quetiapine XR; 1.4%, placebo group) and thyroid stimulating hormone (4.7%, quetiapine XR; 0%, placebo group). An adverse event

  1. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation.

    Science.gov (United States)

    Franek, F; Jarlfors, A; Larsen, F; Holm, P; Steffansen, B

    2015-09-18

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq(®), an extended release formulation (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp(®)) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus), respectively. Desvenlafaxine apparent permeability (Papp) at varying apical pH was investigated using the Caco-2 cell line and extrapolated to effective intestinal permeability (Peff) in human duodenum, jejunum, ileum and colon. Desvenlafaxine pKa-values and octanol-water partition coefficients (Do:w) were determined experimentally. Due to predicted rapid dissolution after IRF administration, desvenlafaxine was predicted to be available for permeation in the duodenum. Desvenlafaxine Do:w and Papp increased approximately 13-fold when increasing apical pH from 5.5 to 7.4. Desvenlafaxine Peff thus increased with pH down the small intestine. Consequently, desvenlafaxine absorption from an IRF appears rate-limited by low Peff in the upper small intestine, which "delays" the predicted

  2. Steady-state pharmacokinetics of once-daily cyclobenzaprine extended release: a randomized, double-blind, 2-period crossover study in healthy volunteers.

    Science.gov (United States)

    Darwish, Mona; Hellriegel, Edward T

    2011-06-01

    The single-dose pharmacokinetic profile of cyclobenzaprine extended-release (CER) has been previously characterized and compared with the pharmacokinetics of cyclobenzaprine immediate-release (CIR) administered 3 times daily for 3 doses. The objective of this study was to characterize the multiple-dose pharmacokinetic properties of once-daily CER 30 mg and CIR 10 mg TID formulations in healthy volunteers. In this double-blind, single-center, 2-period crossover study, healthy subjects were randomized to dosing sequences with once-daily CER 30 mg or CIR 10 mg TID for 7 days. Subjects crossed over to the alternative regimen following a 14-day washout period. Pharmacokinetic assessments at steady state included area under the plasma cyclobenzaprine concentration-time curve over the dosing interval (AUC(0-τ,ss)), peak plasma cyclobenzaprine concentration (C(max,ss)), time to observed C(max) (T(max,ss)), observed minimum cyclobenzaprine concentration (C(min,ss)), average cyclobenzaprine concentration (C(avg,ss)), accumulation ratio (R(ac)), and terminal elimination half-life (t(½)). Tolerability and safety assessments were conducted. A total of 36 subjects were randomized; 34 completed both dosing periods (1 subject was lost to follow-up, 1 withdrew consent). Steady state was reached for CER 30 mg on day 7. Mean C(max,ss), C(min,ss), and C(avg,ss) were 41.1, 21.4, and 31.4 ng/mL, respectively. The median T(max,ss) for CER 30 mg was 7.0 hours, with a mean t(½) of 34.8 hours. At steady state, CER produced a sustained plasma cyclobenzaprine concentration with a single peak in plasma concentration during the 24-hour dose interval. The R(ac) for CER was 2.65. Because of a protocol violation (insufficient data), no steady-state pharmacokinetic assessments could be performed for CIR. Most adverse events were mild or moderate in intensity. Somnolence was the most frequently reported adverse event (100% of subjects) in those receiving CER, followed by dry mouth (58

  3. Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

    Directory of Open Access Journals (Sweden)

    Hale ME

    2013-05-01

    Full Text Available Martin E Hale,1 Srinivas R Nalamachu,2 Arif Khan,3 Michael Kutch4,* 1Gold Coast Research, LLC, Weston, FL, USA; 2International Clinical Research Institute, Overland Park, KS, USA; 3MedNorthwest Clinical Research Center, Bellevue, WA, USA; Duke University Medical Center, Durham, NC, USA; 4Applied Clinical Intelligence, LLC, Bala Cynwyd, PA, USA *Affiliation at the time this work was completed. Michael Kutch is currently affiliated with Cytel Inc, Chesterbrook, PA, USA Purpose: To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER during dose conversion and titration. Patients and methods: A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio, and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs and serious AEs. Results: Mean (standard deviation final daily dose of OROS hydromorphone ER was 37.5 (17.8 mg. Mean (standard error of the mean [SEM] numeric rating scale scores decreased from 6.6 (0.1 at screening to 4.3 (0.1 at the final titration visit (mean [SEM] change, -2.3 [0.1], representing a 34.8% reduction. Mean (SEM change in Patient Global Assessment was -0.6 (0.1, and mean change (SEM in the Roland–Morris Disability Questionnaire was -2.8 (0.3. Patients achieving a stable dose showed greater improvement

  4. Comparison of fesoterodine and tolterodine extended release for the treatment of overactive bladder: a head-to-head placebo-controlled trial.

    Science.gov (United States)

    Herschorn, Sender; Swift, Steven; Guan, Zhonghong; Carlsson, Martin; Morrow, Jon D; Brodsky, Marina; Gong, Jason

    2010-01-01

    To compare the efficacy and tolerability of fesoterodine 8 mg with tolterodine extended-release (ER) 4 mg and placebo in a randomized clinical trial of patients with an overactive bladder (OAB). In this 12-week double-blind, double-dummy, placebo-controlled, randomized clinical trial, eligible patients reported OAB symptoms for > or = 3 months and recorded > or = 8 voids and > or = 1 urgency urinary incontinence (UUI) episode per 24 h in 3-day bladder diaries at baseline. Patients were randomized in a 2:2:1 ratio to fesoterodine (4 mg for 1 week then 8 mg for 11 weeks); tolterodine ER 4 mg; or placebo (with sham dose escalation for tolterodine ER and placebo). Endpoints were changes from baseline to week 12 in UUI episodes (primary endpoint), total and nocturnal voids, urgency episodes, severe urgency episodes, and frequency-urgency sum per 24 h; mean voided volume per void (MVV); and the OAB questionnaire (OAB-q), Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS). Safety and tolerability were assessed and summarized over the 12-week study period. Fesoterodine (636 patients) significantly improved UUI episodes at week 12 (primary endpoint) compared with tolterodine ER (641 patients; P = 0.017) and placebo (313 patients; P Fesoterodine also produced significantly greater improvements than tolterodine ER in MVV (P = 0.005). Fesoterodine significantly improved all diary endpoints compared with placebo (P fesoterodine (64%) than with tolterodine ER (57%; P = 0.015) and placebo (45%; P fesoterodine than placebo (all P fesoterodine group, 16% and 4% in the tolterodine ER group, and 6% and 3% with placebo, respectively. Discontinuations due to treatment-emergent adverse events were 6%, 4% and 2% in the fesoterodine, tolterodine ER, and placebo groups, respectively. In patients with OAB, fesoterodine 8 mg showed superior efficacy over tolterodine ER 4 mg and placebo in reducing UUI episodes (primary endpoint) and in improving most patient

  5. Drug-Drug Interaction Studies of Paliperidone and Divalproex Sodium Extended-Release Tablets in Healthy Participants and Patients with Psychiatric Disorders.

    Science.gov (United States)

    Remmerie, Bart; Ariyawansa, Jay; De Meulder, Marc; Coppola, Danielle; Berwaerts, Joris

    2016-06-01

    The objective of these 2 phase 1, open-label, 2-treatment, single-sequence studies was to evaluate the effect of repeated oral doses of divalproex sodium extended-release (ER) on the pharmacokinetics (PK) of a single dose of paliperidone ER in healthy participants (study 1), and the effect of multiple doses of paliperidone ER on the steady-state PK of valproic acid (VPA) in patients with psychiatric disorders (study 2), respectively. In study 1 healthy participants received, in a fixed sequential order, treatment A, paliperidone ER 12 mg (day 1); treatment B, VPA 1000 mg (2 × 500 mg divalproex sodium ER) once daily (days 5 to 18) and paliperidone ER 12 mg (day 15). In study 2 patients received treatment A, VPA (days 1-7); treatment B, VPA + paliperidone ER 12 mg (days 8-12). Divalproex sodium ER doses (study 2) were individualized such that systemic therapeutic VPA exposure from prior treatment was maintained on entry into the study. PK assessments were performed at prespecified time points (paliperidone days 1 and 15 [study 1]; VPA days 7 and 12 [study 2]). The oral bioavailability of paliperidone was increased by an estimated 51% (Cmax ) and 51%-52% (AUCs) when coadministered with divalproex sodium ER. No effect on the steady-state plasma concentration of VPA was observed following repeated coadministration with paliperidone ER: the 90%CI around the VPA exposure ratios for the 2 treatments was within the 80%-125% bioequivalence criteria for Cmax,ss and AUCτ . Both VPA and paliperidone ER were well tolerated, and no new safety concerns were identified.

  6. Comparison of the pharmacokinetics of venlafaxine extended release and desvenlafaxine in extensive and poor cytochrome P450 2D6 metabolizers.

    Science.gov (United States)

    Preskorn, Sheldon; Patroneva, Albena; Silman, Heather; Jiang, Qin; Isler, Jennifer A; Burczynski, Michael E; Ahmed, Saeeduddin; Paul, Jeffrey; Nichols, Alice I

    2009-02-01

    The goal of this study was to evaluate the impact of cytochrome P450 2D6 extensive metabolizer (EM) or poor metabolizer (PM) status on the pharmacokinetics of single doses of venlafaxine extended release (ER) and desvenlafaxine (administered as desvenlafaxine succinate) in healthy adults. In an open-label, crossover study, 14 healthy volunteers (aged 18-55 years; 7 EMs and 7 PMs) received, in randomized sequence, single doses of venlafaxine ER 75 mg/d or desvenlafaxine 100 mg/d. Cytochrome P450 2D6 genotyping was performed, and plasma drug levels were measured. The arithmetic means and standard deviation (SD) for area under the plasma concentration-versus-time curve (AUC) and peak plasma concentration (Cmax) were calculated. Comparisons of AUC and Cmax between cytochrome P450 2D6 EMs and PMs were calculated using a Wilcoxon exact test. After administration of venlafaxine ER, mean Cmax and AUC of venlafaxine were significantly greater in PMs compared with EMs, whereas mean Cmax and AUC of its metabolite, desvenlafaxine, were significantly lower for PMs than for EMs (P = 0.001, all comparisons). In contrast, mean Cmax and AUC of desvenlafaxine after administration of desvenlafaxine were comparable between EMs and PMs. Cytochrome P450 2D6 genetic polymorphisms had no discernible impact on exposure to desvenlafaxine after desvenlafaxine administration; in contrast, compared with an EM phenotype, a PM phenotype had a significant effect on venlafaxine and desvenlafaxine plasma concentrations after venlafaxine ER administration. This reduced pharmacokinetic variability of desvenlafaxine may translate into better uniformity of response for patients receiving desvenlafaxine versus venlafaxine, but additional studies are required to test this hypothesis.

  7. NIDA Clinical Trials Network CTN-0051, Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment (X:BOT): Study Design and Rationale

    Science.gov (United States)

    Lee, Joshua D.; Nunes, Edward V.; Novo, Patricia; Bailey, Genie L.; Brigham, Gregory S.; Cohen, Allan J.; Fishman, Marc; Ling, Walter; Lindblad, Robert; Shmueli-Blumberg, Dikla; Stablein, Don; May, Jeanine; Salazar, Dagmar; Liu, David; Rotrosen, John

    2017-01-01

    Introduction For opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays. Long-term abstinence is rarely achieved; many patients relapse and overdose after detoxification. Methadone, buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) can prevent opioid relapse but are underutilized. This study is intended to develop an evidence-base to help patients and providers make informed choices and to foster wider adoption of relapse-prevention pharmacotherapies. Methods The National Institute on Drug Abuse's Clinical Trials Network (CTN) study CTN-0051, X:BOT, is a comparative effectiveness study of treatment for 24 weeks with XR-NTX, an opioid antagonist, versus BUP-NX, a high affinity partial opioid agonist, for opioid dependent patients initiating treatment at 8 short-term residential (detoxification) units and continuing care as outpatients. Up to 600 participants are randomized (1:1) to XR-NTX or BUP-NX. Results The primary outcome is time to opioid relapse (i.e., loss of persistent abstinence) across the 24-week treatment phase. Differences between arms in the distribution of time-to-relapse will be compared (construction of the asymptotic 95% CI for the hazard ratio of the difference between arms). Secondary outcomes include proportions retained in treatment, rates of opioid abstinence, adverse events, cigarette, alcohol, and other drug use, and HIV risk behaviors; opioid cravings, quality of life, cognitive function, genetic moderators, and cost effectiveness. Conclusions XR-NTX and BUP-NX differ considerably in their characteristics and clinical management; no studies to date have compared XR-NTX with buprenorphine maintenance. Study design choices and compromises inherent to a comparative effectiveness trial of distinct treatment regimens are reviewed. PMID:27521809

  8. Near-infrared spectroscopic analysis of the breaking force of extended-release matrix tablets prepared by roller-compaction: influence of plasticizer levels and sintering temperature.

    Science.gov (United States)

    Dave, Vivek S; Fahmy, Raafat M; Hoag, Stephen W

    2015-06-01

    The aim of this study was to investigate the feasibility of near-infrared (NIR) spectroscopy for the determination of the influence of sintering temperature and plasticizer levels on the breaking force of extended-release matrix tablets prepared via roller-compaction. Six formulations using theophylline as a model drug, Eudragit® RL PO or Eudragit® RS PO as a matrix former and three levels of TEC (triethyl citrate) as a plasticizer were prepared. The powder blend was roller compacted using a fixed roll-gap of 1.5 mm, feed screw speed to roller speed ratio of 5:1 and roll pressure of 4 MPa. The granules, after removing fines, were compacted into tablets on a Stokes B2 rotary tablet press at a compression force of 7 kN. The tablets were thermally treated at different temperatures (Room Temperature, 50, 75 and 100 °C) for 5 h. These tablets were scanned in reflectance mode in the wavelength range of 400-2500 nm and were evaluated for breaking force. Tablet breaking force significantly increased with increasing plasticizer levels and with increases in the sintering temperature. An increase in tablet hardness produced an upward shift (increase in absorbance) in the NIR spectra. The principle component analysis (PCA) of the spectra was able to distinguish samples with different plasticizer levels and sintering temperatures. In addition, a 9-factor partial least squares (PLS) regression model for tablets containing Eudragit® RL PO had an r(2) of 0.9797, a standard error of calibration of 0.6255 and a standard error of cross validation (SECV) of 0.7594. Similar analysis of tablets containing Eudragit® RS PO showed an r(2) of 0.9831, a standard error of calibration of 0.9711 and an SECV of 1.192.

  9. Long-term tolerability of tolterodine extended release in children 5-11 years of age: results from a 12-month, open-label study.

    Science.gov (United States)

    Nijman, Rien J M; Borgstein, Niels G; Ellsworth, Pamela; Siggaard, Charlotte

    2007-11-01

    To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI). This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI suggestive of detrusor overactivity (>/=1 diurnal incontinence episode per 24h for >/=5 of 7 d) and >/=6 voids per 24h at baseline and had completed the 12-wk double-blind study. Patients received tolterodine ER (2mg once daily) for 12 mo. The primary end points were the incidence and severity of adverse events (AEs) and the incidence and reasons for withdrawals. Visits were scheduled at 3, 6, 9, and 12 mo, and investigators were instructed to report all AEs. At 6 and 12 mo, vital signs were recorded and a physical examination was performed. A total of 318 patients were enrolled (double-blind tolterodine ER, n=221; placebo, n=97). The majority of patients were white (90%), mean+/-SD age was 7.6+/-1.5 yr, and 54% were boys. Forty-nine percent of patients reported >/=1 AE during the study, similar to that observed in the preceding 12-wk study (42%). The most frequent AEs were urinary tract infection (7%), nasopharyngitis (5%), headache (5%), and abdominal pain (4%); 111 (35%) patients withdrew. The most common reasons for withdrawal were lack of efficacy (12%), symptom improvement (8%), and withdrawn consent (6%). Ten patients (3%) withdrew because of AEs. Long-term treatment with tolterodine ER was well tolerated in children with UUI.

  10. Single-dose pharmacokinetics of once-daily cyclobenzaprine extended release 30 mg versus cyclobenzaprine immediate release 10 mg three times daily in healthy young adults : a randomized, open-label, two-period crossover, single-centre study.

    Science.gov (United States)

    Darwish, Mona; Hellriegel, Edward T; Xie, Fang

    2008-01-01

    Cyclobenzaprine immediate release (CIR) has shown efficacy in the treatment of muscle spasm associated with acute, painful musculoskeletal conditions. An extended-release formulation of cyclobenzaprine (CER) has been developed to provide effective muscle spasm relief with once-daily dosing. The objective of this study was to compare the pharmacokinetics of CER and CIR. This was a single-centre study of 18 healthy young adults (aged 18-45 years). Healthy volunteers were assigned to receive either a single dose of CER 30 mg or three doses of CIR 10 mg on days 1 and 15 (separated by a 14-day washout) in an open-label, two-period crossover study. Pharmacokinetic parameters were monitored through 168 hours after the last dose in each dose period; adverse events (AEs) were monitored during the study through 3 weeks after the last dose of study drug. Cyclobenzaprine was administered as a single oral 30 mg dose of CER or three 10 mg oral doses of CIR given every 8 hours over 24 hours. Statistical tests were conducted against a two-sided alternative hypothesis at a 0.05 level of significance with equivalence limits of 80% and 125%. Measures included area under the plasma cyclobenzaprine concentration versus time curve (AUC) to 168 hours and infinity, maximum plasma cyclobenzaprine concentration (C(max)), and time to observed C(max) (t(max)). Eighteen subjects were randomized and 17 completed both periods of the study. CER exhibited a consistent concentration-time profile with a single peak, in contrast to the pharmacokinetic profile for CIR, which displayed multiple peaks and troughs over the 24-hour period. The pharmacokinetic profile of CER 30 mg was characterized by an absorption phase with a median t(max) of approximately 6 hours, compared with the initial peak of CIR (following the first dose) of about 4 hours. Mean plasma concentrations at 4 hours were comparable (12.1 ng/mL for CER; 12.4 ng/mL for CIR). Systemic cyclobenzaprine exposure (AUC and C(max)) was similar

  11. Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine

    DEFF Research Database (Denmark)

    Jeppesen, U; Gram, L F; Vistisen, K

    1996-01-01

    OBJECTIVE: The purpose of this pharmacokinetic study was to investigate the dose-dependent inhibition of model substrates for CYP2D6, CYP2C19 and CYP1A2 by four marketed selective serotonin reuptake inhibitors (SSRIs): citalopram, fluoxetine, fluvoxamine and paroxetine. METHODS: The study...... by sparteine (CYP2D6), mephenytoin (CYP2C19) and caffeine (CYP1A2) tests. Fluoxetine was given at 3-week intervals because of the long half-life of fluoxetine and its metabolite norfluoxetine. Citalopram, fluoxetine and paroxetine were given in doses of 10, 20, 40 and 80 mg and fluvoxamine was given in doses...... after fluoxetine intake, although no volunteers changed phenotype from extensive metabolisers to poor metabolisers. Three of the six volunteers changed phenotype from extensive metabolisers to poor metabolisers after intake of 40 or 80 mg paroxetine. There was a statistically significant increase...

  12. 帕利哌酮缓释片用于精神分裂症复发的研究进展%Research progress of paliperidone extended-release tablet applied in schizophrenia relapse

    Institute of Scientific and Technical Information of China (English)

    黄宇

    2014-01-01

    帕利哌酮缓释片是目前临床常用的一种非典型抗精神病药物,临床作用机制是主要通过阻断全部的5-羟色胺2A(5-HT2A)受体和部分多巴胺D2(DA2)受体,进而发挥抗精神病的作用。近年来,随着帕利哌酮缓释片在临床上被广泛应用,许多临床研究提示帕利哌酮缓释片可有效控制精神分裂症患者的阳性症状、改善阴性症状和认知损害、提高患者的耐受性和依从性。帕利哌酮缓释片起效快,且可有效改善对其他非典型抗精神病药治疗无效患者的临床效果,为精神分裂症患者的全面康复提供有效的治疗。近年来的统计观察发现,帕利哌酮缓释片应用于急性期及首发精神分裂症患者的临床效果较好,临床治愈率满意,但帕利哌酮缓释片对精神分裂症复发的效果如何尚未报道。本院通过对住院或门诊复发精神分裂症患者应用帕利哌酮缓释片的观察,评价帕利哌酮缓释片治疗精神分裂症复发的临床效果。本研究对帕利哌酮缓释片治疗精神分裂症复发的研究进行综述。%Paliperidone extended-release tablet is used as a common atypical antipsychotic drugs,and its clinical mechanism of action is mainly blocking all 5-HT2A receptor and partial DA2 receptor in order to play the role of anti psychotic.In recent years,with the extensive use of paliperidone extended-release tablet in the clinic,many study showed that paliperidone extended-release tablet can effectively control the positive symptoms of patients with schizophrenia,improve negative symptoms and cognitive impairment and improve the tolerance and compliance pa-tients.Paliperidone extended-release tablet with rapid action can effectively improve the clinical efficacy of other pa-tients treated inefficiently by other atypical antipsychotics therapy,and it can provide effective treatment for the com-prehensive rehabilitation of patients with schizophrenia

  13. Development of a Physiologically Relevant Population Pharmacokinetic in Vitro-in Vivo Correlation Approach for Designing Extended-Release Oral Dosage Formulation.

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    Kim, Tae Hwan; Shin, Soyoung; Bulitta, Jürgen B; Youn, Yu Seok; Yoo, Sun Dong; Shin, Beom Soo

    2017-01-03

    Establishing a level A in vitro-in vivo correlation (IVIVC) for a drug with complex absorption kinetics is challenging. The objective of the present study was to develop an IVIVC approach based on population pharmacokinetic (POP-PK) modeling that incorporated physiologically relevant absorption kinetics. To prepare three extended release (ER) tablets of loxoprofen, three types of hydroxypropyl methylcellulose (HPMC 100, 4000, and 15000 cps) were used as drug release modifiers, while lactose and magnesium stearate were used as the diluent and lubricant, respectively. An in vitro dissolution test in various pH conditions showed that loxoprofen dissolution was faster at higher pH. The in vivo pharmacokinetics of loxoprofen was assessed following oral administration of the different loxoprofen formulations to Beagle dogs (n = 22 in total). Secondary peaks or shoulders were observed in many of the individual plasma concentration vs time profiles after ER tablet administration, which may result from secondary absorption in the intestine due to a dissolution rate increase under intestinal pH compared to that observed at stomach pH. In addition, in vivo oral bioavailability was found to decrease with prolonged drug dissolution, indicating site-specific absorption. Based on the in vitro dissolution and in vivo absorption data, a POP-PK IVIVC model was developed using S-ADAPT software. pH-dependent biphasic dissolution kinetics, described using modified Michaelis-Menten kinetics with varying Vmax, and site-specific absorption, modeled using a changeable absorbed fraction parameter, were applied to the POP-PK IVIVC model. To experimentally determine the biphasic dissolution profiles of the ER tablets, another in vitro dissolution test was conducted by switching dissolution medium pH based on an in vivo estimate of gastric emptying time. The model estimated, using linear regression, that in vivo initial maximum dissolution rate (Vmax(0)in vivo) was highly correlated (r(2) > 0

  14. Presence of Tablet Remnants of Nevirapine Extended-Release in Stools and Its Impact on Virological Outcome in HIV-1-Infected Patients: A Prospective Cohort Study.

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    Yi-Chieh Lee

    Full Text Available Nevirapine extended-release (NVP-XR taken once daily remains an effective antiretroviral agent for patients infected with HIV-1 strains that do not harbor resistance mutations. Presence of tablet remnants of NVP XR in stools was reported in 1.19% and 3.05% of subjects in two clinical trials. However, the prevalence may have been underestimated because the information was retrospectively collected in the studies.Between April and December 2014, we prospectively inquired about the frequency of noticing tablet remnants of NVP XR in stools in HIV-1-infected patients who switched to antiretroviral regimens containing NVP XR plus 2 nucleos(tide reverse-transcriptase inhibitors. Patients were invited to participate in therapeutic drug monitoring of plasma concentrations of NVP 12 or 24 hours after taking the previous dose (C12 and C24, respectively of NVP XR using high-performance liquid chromatography. The information on clinical characteristics, including plasma HIV RNA load and CD4 lymphocyte count, at baseline and during follow-up was recorded.During the 9-month study period, 272 patients switched to NVP XR-based regimens and 60 (22.1% noticed tablet remnants of NVP XR in stools, in whom 54.2% reported noticing the tablet remnants at least once weekly. Compared with patients who did not notice tablet remnants, those who noticed tablet remnants had a higher mean CD4 lymphocyte count (629 vs 495 cells/mm3, P = 0.0002 and a similar mean plasma HIV RNA load (1.57 vs 1.61 log10 copies/mL, P = 0.76 on switch. At about 12 and 24 weeks after switch, patients who noticed tablet remnants continued to have a similar mean plasma HIV RNA load (1.39 vs 1.43 log10 copies/mL, P = 0.43; and 1.30 vs 1.37 log10 copies/mL, P = 0.26, respectively, but had a lower median NVP C12 (3640 vs 4730 ng/mL, P = 0.06, and a similar median NVP C24 (3220 vs 3330 ng/ml, P = 0.95 when compared with those who did not notice tablet remnants.The presence of tablet remnants of NVP XR in

  15. An open-label, flexible-dose study of paliperidone extended-release in Chinese patients with first-onset psychosis

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    Si TM

    2015-01-01

    Full Text Available TianMei Si,1 QingRong Tan,2 KeRang Zhang,3 Yang Wang,4 Qing Rui4 1Peking University Institute of Mental health, Key Laboratory of Mental Health, Ministry of Health (Peking University, Beijing, 2Fourth Military Medical University, First Hospital, Xi’an, 3Shanxi Medical University, First Hospital, Shanxi, 4Janssen Research and Development, Beijing, People’s Republic of China Background: Antipsychotic medications facilitate the improvement of psychotic symptoms in patients with first-episode psychosis. Paliperidone extended-release (pali-ER, an atypical anti­psychotic, was assessed for efficacy and safety in Chinese patients with first-episode psychosis. Methods: In this 8-week, open-label, single-arm, multicenter study, patients with first-episode psychosis (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and a Positive and Negative Syndrome Scale (PANSS total score ≥70 were treated with flexible-dose pali-ER tablets (3–12 mg/day. The primary efficacy endpoint was the percentage of patients with an increase of ≥8 points in Personal and Social Performance (PSP score from baseline to day 56 (8 weeks. Secondary endpoints included reduction in PANSS total score, improvement in Clinical Global Impression-Severity score, PSP score, Subjective Well-being under Neuroleptics Scale score, and relationship between duration of untreated psychosis and PANSS or PSP. Incidences of treatment-emergent adverse events were used to evaluate safety.Results: Overall, 283 of 294 patients (96% achieved a ≥8-point increase in PSP (primary endpoint, analysis set. For the secondary efficacy endpoints, 284/306 patients (93% had a ≥30% reduction in PANSS total score; 266/306 patients (87% achieved a ≤3 Clinical Global Impression-Severity scale score, and 218/294 patients (74% had a PSP score ≥71. The Subjective Well-being under Neuroleptics Scale score was improved from a baseline mean of 72.7 to 94.7 at endpoint. There was a

  16. Superior efficacy of fesoterodine over tolterodine extended release with rapid onset: a prospective, head-to-head, placebo-controlled trial.

    Science.gov (United States)

    Kaplan, Steven A; Schneider, Tim; Foote, Jenelle E; Guan, Zhonghong; Carlsson, Martin; Gong, Jason

    2011-05-01

    • To show the superior efficacy of fesoterodine over tolterodine extended release (ER) in a placebo-controlled overactive bladder (OAB) trial with predefined treatment comparisons for both diary measures and patient-reported outcomes. • In this 12-week, double-blind, double-dummy trial, subjects reporting >1 urgency urinary incontinence (UUI) episode and ≥8 micturitions per 24 h at baseline were randomized to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks), tolterodine ER 4 mg, or placebo. • Subjects completed 3-day bladder diaries, the Patient Perception of Bladder Condition (PPBC) and the Urgency Perception Scale (UPS) at baseline and weeks 1, 4 and 12 and the OAB Questionnaire at baseline and week 12. • A total of 2417 subjects were randomized. At week 12, fesoterodine 8 mg showed superiority over tolterodine ER 4 mg and placebo on UUI episodes (primary endpoint), micturitions, urgency and most other diary endpoints, and on the PPBC, UPS and all OAB Questionnaire scales and domains (all P fesoterodine 8 mg over tolterodine ER 4 mg was seen as early as week 4 (3 weeks after escalation to fesoterodine 8 mg). At week 1, fesoterodine 4 mg was superior to placebo on most diary variables, the PPBC and the UPS (all P fesoterodine, 13% and 3% with tolterodine ER, and 5% and 2% with placebo. • Discontinuation rates as a result of adverse events were 5%, 3% and 2% for fesoterodine, tolterodine ER and placebo, respectively. • In this randomized study, which is the largest to compare antimuscarinic efficacy performed to date, fesoterodine 8 mg was superior to tolterodine ER 4 mg for UUI episodes, micturitions and urgency episodes, as well as for self-reported patient assessments of bladder-related problems, urgency, symptom bother and health-related quality of life. • The superiority of fesoterodine 8 mg over tolterodine ER 4 mg was observed as early as 3 weeks after escalation from fesoterodine 4 mg for most outcomes. These data may have important

  17. Extended-Release Niacin Versus Fenofibrate in HIV-Infected Participants With Low High-Density Lipoprotein Cholesterol: Effects on Endothelial Function, Lipoproteins, and Inflammation.

    Science.gov (United States)

    Dubé, Michael P; Komarow, Lauren; Fichtenbaum, Carl J; Cadden, Joseph J; Overton, Edgar T; Hodis, Howard N; Currier, Judith S; Stein, James H

    2015-09-01

    Low levels of high-density lipoprotein cholesterol (HDL-C) are common in individuals with human immunodeficiency virus (HIV) infection, persist during antiretroviral therapy (ART), and are associated with increased cardiovascular disease (CVD) risk. Virologically controlled participants without CVD on stable ART with low HDL-C (men 150 mg/dL were randomized to receive open-label extended-release niacin 1500 mg/day with aspirin 325 mg/day or fenofibrate 200 mg/day for 24 weeks. The primary endpoint was the week 24 within-arm change in brachial artery flow-mediated dilation (FMD) in participants with complete follow-up scans. Of 99 participants, 74 had complete data (35 niacin, 39 fenofibrate). Median age was 45 years, 77% were male, median CD4(+) count was 561 cells/µL, and brachial FMD was 4.2%. Median HDL-C was 32 mg/dL for men and 38 mg/dL for women, low-density lipoprotein cholesterol was 103 mg/dL, and triglycerides were 232 mg/dL. In men, HDL-C increased a median of 3 mg/dL with niacin and 6.5 mg/dL with fenofibrate (P < .001 for both). In women, HDL-C increased a median of 16 mg/dL with niacin and 8 mg/dL with fenofibrate (P = .08 for both). After 24 weeks, there was no significant change in FMD in either arm; the median (interquartile range) change was +0.6% (-1.6 to 2.3) with niacin (P = .28) and +0.5% (-1.0 to 3.0) with fenofibrate (P = .19). Neither treatment significantly affected C-reactive protein, interleukin 6, or D-dimer levels. Despite improvements in lipids, niacin or fenofibrate treatment for 24 weeks did not improve endothelial function or inflammatory markers in participants with well-controlled HIV infection and low HDL-C. NCT01426438. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. An open-label, prospective study to evaluate social function and overall improvement of extended-release paliperidone treatment in Thai schizophrenia patients

    Directory of Open Access Journals (Sweden)

    Charnsil C

    2013-08-01

    Full Text Available Chawanun Charnsil,1 Salinee Vongpanich21Department of Psychiatry, Chiang Mai University, Chiang Mai, Thailand; 2Medical Affairs Department, Janssen-Cilag, Bangkok, ThailandBackground: Previous studies with extended-release (ER paliperidone have reported an effective outcome in terms of personal and social functioning improvement and also reported schizophrenia symptom improvement. The main objectives of this study were to further investigate improvements in symptom control and social functioning of paliperidone ER and acknowledge the safety profile of paliperidone ER in Thai patients with schizophrenia.Patients and methods: Patients with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders criteria were allowed flexible 3–12 mg/day dosing during the 10-week study duration. Patients were interviewed and assessed in social functioning using the Personal and Social Performance (PSP scale. Patients were also rated on overall severity of illness using the Clinical and Global Impressions – Severity (CGI-S scale.Results: In total, 40 patients were enrolled, 80% of enrolled patients (n = 32 completed the 10-week study period. Thirty-eight eligible patients were included in the intention-to-treat analysis set (male 39.5%, female 60.5%. One patient was lost to follow-up without postbaseline-efficacy measurements. Another patient was terminated early due to a change in diagnosis during the trial. Statistically significant improvements from baseline in PSP total score were observed at all time points. Clinically relevant improvement in PSP (increase of at least one 10-point category was observed in 47.40% of patients at end point. Improvement in CGI-S was observed at end point (P < 0.001. The mean reduction ± standard deviation at end point in CGI-S was 0.8 ± 1.04 (95% confidence interval 0.48–1.16. The most commonly reported adverse events (≥5% of patients were daytime drowsiness (15% and headache (15%. Three subjects

  19. Mouse strain differences in immobility and sensitivity to fluvoxamine and desipramine in the forced swimming test: analysis of serotonin and noradrenaline transporter binding.

    Science.gov (United States)

    Sugimoto, Yumi; Kajiwara, Yoshinobu; Hirano, Kazufumi; Yamada, Shizuo; Tagawa, Noriko; Kobayashi, Yoshiharu; Hotta, Yoshihiro; Yamada, Jun

    2008-09-11

    Strain differences in immobility time in the forced swimming test were investigated in five strains of mice, namely, ICR, ddY, C57BL/6, DBA/2 and BALB/c mice. There were significant strain differences. The immobility times of ICR, ddY and C57BL/6 mice were longer than those of DBA/2 and BALB/c mice. Immobility times were not significantly related to locomotor activity in these strains. There were also differences in sensitivity to the selective serotonin reuptake inhibitor (SSRI) fluvoxamine. In ICR, ddY and C57BL/6 mice, fluvoxamine did not affect immobility time, while it reduced the immobility time of DBA/2 and BALB/c mice dose-dependently. The noradrenaline reuptake inhibitor desipramine decreased immobility time in all strains of mice. Serotonin (5-HT) transporter binding in the brains of all five strains of mice was also investigated. Analysis of 5-HT transporter binding revealed significant strain differences, being lower in DBA/2 and BALB/c mice than in other strains of mice. The amount of 5-HT transporter binding was correlated to baseline immobility time. However, there was no significant relation between noradrenaline transporter binding and immobility time. These results suggest that the duration of baseline immobility depends on the levels of 5-HT transporter binding, leading to apparent strain differences in immobility time in the forced swimming test. Furthermore, differences in 5-HT transporter binding may cause variations in responses to fluvoxamine.

  20. PHARMACOKINETIC AND BIOEQUIVALENCE COMPARISON BETWEEN EXTENDED RELEASE CAPSULES OF VENLAFAXINE HYDROCHLORIDE 150MG: AN OPEN LABEL, BALANCED, RANDOMIZED-SEQUENCE, SINGLE-DOSE, TWO-PERIOD CROSSOVER STUDY IN HEALTHY INDIAN MALE VOLUNTEERS

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    I.Sarath chandiran

    2011-03-01

    Full Text Available This bioequivalence study was designed to determine the pharmacokinetic, bioavailability and bioequivalence of Venlafaxine HCl 150 mg Extended Release Capsules in comparison with Effexor®-XR 150mg Extended Release Capsules after single dose administration under fed conditions in 20 healthy adult male subjects. Therefore the design of an open label, balanced, randomized, two-sequence, single dose, two way crossover study with a washout period of at least 7 days was used.Each volunteer received a 150 mg capsule of the reference or test drug respectively. On the day of dosing, blood samples were collected before dosing and at various time points up to 72 hours after dosing. Analysis of venlafaxine and its metabolite O-Desmethylvenlafaxine concentrations was performed using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS method. The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, Tmax, t1/2 and Kel were analyzed using the non-compartmental model. Drug safety and tolerability were assessed.The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, Tmax, t1/2 and Kel were analyzed using the non-compartmental model. Drug safety and tolerability were assessed. The primary pharmacokinetic parameters (Cmax, AUC0-t and AUC0-inf 90%CI were within the 80 to 125% interval required for bioequivalence as stipulated in the current regulations of the USFDA acceptance criteria. The geometric mean ratios (Test/Reference between the two products of extended-release venlafaxine capsule under fed condition were 104.91% (92.86%-118.53% and 114.41% (103.43%-124.55% for Cmax ratios, 102.24% (95.95%-108.94% and 105.27% (96.76%-114.53% for AUC0-t ratios and 101.66% (95.73%-107.97% and 104.71% (96.13%-114.05% for AUC0-inf ratios of Venlafaxine and its metabolite O-Desmethylvenlafaxine (ODV respectively. 20 volunteers had completed both treatment periods. There was no significant difference of the Tmax parameter between the two

  1. Nanoformulated antiretroviral drug combinations extend drug release and antiretroviral responses in HIV-1-infected macrophages: implications for neuroAIDS therapeutics.

    Science.gov (United States)

    Nowacek, Ari S; McMillan, JoEllyn; Miller, Reagan; Anderson, Alec; Rabinow, Barrett; Gendelman, Howard E

    2010-12-01

    We posit that improvements in pharmacokinetics and biodistributions of antiretroviral therapies (ART) for human immunodeficiency virus type one-infected people can be achieved through nanoformulationed drug delivery systems. To this end, we manufactured nanoparticles of atazanavir, efavirenz, and ritonavir (termed nanoART) and treated human monocyte-derived macrophages (MDM) in combination therapies to assess antiretroviral responses. This resulted in improved drug uptake, release, and antiretroviral efficacy over monotherapy. MDM rapidly, within minutes, ingested nanoART combinations, at equal or similar rates, as individual formulations. Combination nanoART ingested by MDM facilitated individual drug release from 15 to >20 days. These findings are noteworthy as a nanoART cell-mediated drug delivery provides a means to deliver therapeutics to viral sanctuaries, such as the central nervous system during progressive human immunodeficiency virus type one infection. The work brings us yet another step closer to realizing the utility of nanoART for virus-infected people.

  2. Development and validation of stability indicating method for the quantitative determination of venlafaxine hydrochloride in extended release formulation using high performance liquid chromatography

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    Jaspreet Kaur

    2010-01-01

    Full Text Available Objective : Venlafaxine,hydrochloride is a structurally novel phenethyl bicyclic antidepressant, and is usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI but it has been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor. It inhibits the reuptake of dopamine. Venlafaxine HCL is widely prescribed in the form of sustained release formulations. In the current article we are reporting the development and validation of a fast and simple stability indicating, isocratic high performance liquid chromatographic (HPLC method for the determination of venlafaxine hydrochloride in sustained release formulations. Materials and Methods : The quantitative determination of venlafaxine hydrochloride was performed on a Kromasil C18 analytical column (250 x 4.6 mm i.d., 5 μm particle size with 0.01 M phosphate buffer (pH 4.5: methanol (40: 60 as a mobile phase, at a flow rate of 1.0 ml/min. For HPLC methods, UV detection was made at 225 nm. Results : During method validation, parameters such as precision, linearity, accuracy, stability, limit of quantification and detection and specificity were evaluated, which remained within acceptable limits. Conclusions : The method has been successfully applied for the quantification and dissolution profiling of Venlafaxine HCL in sustained release formulation. The method presents a simple and reliable solution for the routine quantitative analysis of Venlafaxine HCL.

  3. Development and in vitro evaluation of extended-release theophylline matrix capsules Desenvolvimento e avaliação in vitro de cápsulas de teofilina de liberação prolongada

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    Vanessa Alves Pinheiro

    2007-06-01

    Full Text Available Polymers like cellulose (MethocelTM K100MPRCR, K15MPRCR and E4MCR at different proportions (15-35% were used to slow the release of theophylline (100 mg from capsules. Volumetric method for powder filling capsules was used to prepare the capsules. Drug release from capsules was performed using apparatus 1, at 100 rpm and 900 mL of intestinal medium without enzymes (pH 7.5, at 37 °C, following the USP 28th ed. (Test 8. Dissolution profiles were compared to two batches of commercial extended-release capsules. Capsules compounded with 35% (wt/wt of MethocelTM E4MCR showed dissolution profile according to the official especifications. Similar results were reproduced with other ten compounded batches. Commercial extended-release capsules containing theophylline pellets (100 mg showed quick drug release when submitted to the same test, indicating that, in these conditions, the capsules did not show prolonged release. Mathematical models like zero-order, first-order and Higuchi were applied in kinetic studies of theophylline release from the compounded capsules. Polymers were efficient to control the release of theophylline in capsules involving diffusion and erosion as mechanisms, and that first-order model was the best fitted one for theophylline matrix capsules. These results support that compounded extended-release capsules can be prepared, since the drug release tests can be done.Cápsulas de liberação modificada contendo 100 mg de teofilina foram preparadas com polímeros derivados da celulose (Methocel® K100MPRCR, K15MPRCR e E4MCR em diferentes concentrações, 15-35%, empregando-se o método volumétrico. Estudos de liberação do fármaco foram realizados de acordo com a Farmacopéia Americana 28 ed., (Teste 8, empregando aparato 1, rotação de 100 rpm e temperatura de 37 ºC em 900 mL de meio fluido intestinal sem enzimas (pH 7,5. Os perfis de dissolução foram comparados ao de duas especialidades farmacêuticas comerciais. A formula

  4. Involvement of the 5-HT(1A) receptor in the anti-immobility effects of fluvoxamine in the forced swimming test and mouse strain differences in 5-HT(1A) receptor binding.

    Science.gov (United States)

    Sugimoto, Yumi; Furutani, Sachiko; Kajiwara, Yoshinobu; Hirano, Kazufumi; Yamada, Shizuo; Tagawa, Noriko; Kobayashi, Yoshiharu; Hotta, Yoshihiro; Yamada, Jun

    2010-03-10

    We previously demonstrated the presence of strain differences in baseline immobility time and sensitivity to the selective serotonin reuptake inhibitor (SSRI) fluvoxamine in five strains of mice (ICR, ddY, C57BL, DBA/2 and BALB/c mice). Furthermore, variations in serotonin (5-HT) transporter binding in the brain were strongly related to strain differences in baseline immobility and sensitivity to fluvoxamine. In the present study, we examined the involvement of the 5-HT(1A) receptor in anti-immobility effects in DBA/2 mice, which show high sensitivity to fluvoxamine. The anti-immobility effects of fluvoxamine in DBA/2 mice were inhibited by the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635). However, the 5-HT(1B) receptor antagonist 3-[3-(dimethylamino)propyl]-4-hydroxy-N-[4-(4-pyridinyl)phenyl]benzamide (GR55562), the 5-HT(2) receptor antagonist 6-methyl-1-(methylethyl)-ergoline-8beta-carboxylic acid 2-hydroxy-1-methylpropyl ester (LY 53857), the 5-HT(3) receptor antagonist ondansetron and the 5-HT(4) receptor antagonist 4-amino-5-chloro-2-methoxy-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205,557) did not influence the anti-immobility effects of fluvoxamine in DBA/2 mice. These results suggest that fluvoxamine-induced antidepressant-like effects in DBA/2 mice are mediated by the 5-HT(1A) receptor. We analyzed 5-HT(1A) receptor binding in the brains of five strains of mice. Strain differences in 5-HT(1A) receptor binding were observed. 5-HT(1A) receptor binding in brain was not correlated with baseline immobility time in the five strains of mice examined. These results suggest that, although the anti-immobility effects of fluvoxamine in DBA/2 mice are mediated by the 5-HT(1A) receptor, strain differences in 5-HT(1A) receptor binding are not related to variation in immobility time and responses to fluvoxamine.

  5. Release of azithromycin extended release for oral suspension and evaluation of in vitro-in vivo correlation in beagle dogs%阿奇霉素缓释干混悬剂释放度测定及Beagle犬体内外相关性评价

    Institute of Scientific and Technical Information of China (English)

    阚淑玲; 谢卫锋; 周永强

    2012-01-01

    目的 进行阿奇霉素缓释干混悬剂体外释放度的测定及比格犬体内外相关性评价.方法 按2010版中国药典释放度测定法测定阿奇霉素缓释干混悬剂体外释放度,用液相色谱-串联质谱(LC/MS/MS)法测定阿奇霉素在比格犬体内的血药浓度,并用WinNonlin Professional v5.2进行数据处理.结果 以体内吸收分数(fa)对体外累积释放度(F)进行线性回归,得方程fa=1.1553F-52.931(r=0.9475).结论 体内吸收分数与体外累积释放度具有良好的相关性,阿奇霉素缓释干混悬剂所采用的释放度测定方法合理,可以较好反映体内吸收情况.%Objective To study the release of azithromycin extended release for oral suspension and to evaluate the correlation between in vitro and in vivo in Beagle dogs. Methods Release test method in azithromycin extended release for oral suspension adopted by ChP was used for determination of release in vitro. The concentrations of azithromycin in Beagle plasma were determined by LC/MS/MS. Results The linear equation based on the accumulation( F ) and absorption percentage( fa )was fa = 1. 1553F -52. 931 and the correlation coefficient was 0. 9475. Conclusion To a certain extent,the vitro release test in ChP could reflect the vivo absorption.

  6. Serotonin reuptake inhibition vs. norepinephrine reuptake inhibition: a double-blind differential-therapeutic study with fluvoxamine and oxaprotiline in endogenous and neurotic depressives.

    Science.gov (United States)

    Emrich, H M; Berger, M; Riemann, D; von Zerssen, D

    1987-03-01

    The antidepressive properties of the specific serotonin reuptake inhibitor fluvoxamine and the specific norepinephrine reuptake inhibitor oxaprotiline were investigated in a sequential design with the aim of evaluating the hypothesis that two distinct biochemical subtypes of depression exist. Responders were treated for 7 weeks with the compound to which they had responded. After 1 placebo week, the nonresponders were switched to the alternative compound. An evaluation of the data obtained during the 3-week treatment periods from 24 patients (37 trials) with major depression revealed a highly significant reduction of Hamilton Scores with both compounds, oxaprotiline and fluvoxamine. If the patients with major depression are subdivided into two groups, endogenous depressives and neurotic depressives, there is no significant difference between the therapeutic improvements (both compounds) achieved in the two groups. The data shows that only about 20% of the nonresponders on one compound responded to the alternative drug, whereas 90% of responders (within 3 weeks) were still responders after 7 weeks. The data are at variance with the concept of two distinct biochemical subtypes of depression (serotonergic vs. norepinephrinergic). Dexamethasone suppression tests, performed in 23 patients, gave no prognostic hint as to whether the patients reacted well to drug therapy or not.

  7. Does Extended-Release Liposomal Bupivacaine Better Control Pain Than Bupivacaine After Total Knee Arthroplasty (TKA)? A Prospective, Randomized Clinical Trial.

    Science.gov (United States)

    Schroer, William C; Diesfeld, Paul G; LeMarr, Angela R; Morton, Diane J; Reedy, Mary E

    2015-09-01

    Liposomal bupivacaine periarticular injection (PAI) offers sustained bupivacaine release after TKA, but few prospective independent studies exist. In this prospective, blinded study, liposomal bupivacaine was randomized against bupivacaine and incorporated into a comprehensive multimodal pain management protocol. 111 primary TKAs were randomized to receive PAI: 58 patients received 266 mg (20cc) liposomal bupivacaine mixed with 75 mg (30cc) 0.25% bupivacaine, and 53 patients received 150 mg (60cc) 0.25% bupivacaine. Visual analog pain scores and narcotic use were determined. No pain score differences occurred between study and control patients: Day 1: 4.5/4.6 (P=0.73); Day 2: 4.4/4.8 (P=0.27); or Day 3: 3.5/3.7 (P=0.58). Narcotic use was similar during hospitalization, 51.8/54.2 (P=0.34). The study medication costs $285, and the control medication costs $2.80. This finding does not justify the routine use of liposomal bupivacaine.

  8. Inhibition of the Ca2+ release channel, IP3R subtype 3 by caffeine slows glioblastoma invasion and migration and extends survival

    Science.gov (United States)

    Kang, Sang Soo; Han, Kyung-Seok; Ku, Bo Mi; Lee, Yeon Kyung; Hong, Jinpyo; Shin, Hye Young; Almonte, Antoine G.; Woo, Dong Ho; Brat, Daniel J.; Hwang, Eun Mi; Yoo, Seung Hyun; Chung, Chun Kee; Park, Sung-Hye; Paek, Sun Ha; Roh, Eun Joo; Lee, Sung joong; Park, Jae-Yong; Traynelis, Stephen F.; Lee, C. Justin

    2009-01-01

    Ca2+ signaling is an important determining factor in many cellular processes, especially in cancer cell proliferation, motility and invasion. Glioblastoma is the deadliest brain cancer with its average survival time of less than a year, with the most prominent cellular feature being the ability of these cells to migrate to and invade the neighboring tissue. We hypothesized that disturbing the Ca2+ signaling pathway would decrease the propensity for these cells to migrate. Thus, we investigated the detailed Ca2+ signaling pathway of the glioblastoma cells in response to various receptor tyrosine kinases (RTK) and G-protein coupled receptor (GPCR) agonists. Here we report that caffeine, which is a well-known activator of ryanodine receptors (RyRs), paradoxically inhibits inositol-1, 4, 5-triphospate receptor(IP3R)-mediated Ca2+ increase by selectively targeting IP3R subtype 3(IP3R3), whose mRNA expression is significantly increased in glioblastoma cells. Consequently, by inhibiting IP3R3-mediated Ca2+ release, caffeine was found to inhibit the invasion and migration of various glioblastoma cell lines in scrape motility, Matrigel invasion, soft agar, and brain slice implantation assays. In a mouse xenograft model of glioblastoma, caffeine intake via drinking water greatly increased mean survival duration of subject animals. These findings propose IP3R3 as a novel target for glioblastoma treatment and that caffeine may be a useful adjunct therapy that slows glioblastoma invasion and migration by selectively targeting IP3R3. PMID:20103623

  9. Pharmacokinetics, safety, and efficacy of APF530 (extended-release granisetron) in patients receiving moderately or highly emetogenic chemotherapy: results of two Phase II trials.

    Science.gov (United States)

    Gabrail, Nashat; Yanagihara, Ronald; Spaczyński, Marek; Cooper, William; O'Boyle, Erin; Smith, Carrie; Boccia, Ralph

    2015-01-01

    Despite advances with new therapies, a significant proportion of patients (>30%) suffer delayed-onset chemotherapy-induced nausea and vomiting (CINV) despite use of antiemetics. APF530 is a sustained-release subcutaneous (SC) formulation of granisetron for preventing CINV. APF530 pharmacokinetics, safety, and efficacy were studied in two open-label, single-dose Phase II trials (C2005-01 and C2007-01, respectively) in patients receiving moderately emetogenic chemotherapy or highly emetogenic chemotherapy. In C2005-01, 45 patients received APF530 250, 500, or 750 mg SC (granisetron 5, 10, or 15 mg, respectively). In C2007-01, 35 patients were randomized to APF530 250 or 500 mg SC. Injections were given 30 to 60 minutes before single-day moderately emetogenic chemotherapy or highly emetogenic chemotherapy. Plasma granisetron was measured from predose to 168 hours after study drug administration. Safety and efficacy were also evaluated. APF530 pharmacokinetics were dose proportional, with slow absorption and elimination of granisetron after a single SC dose. Median time to maximum plasma concentration and half-life were similar for APF530 250 and 500 mg in both trials, with no differences between the groups receiving moderately and highly emetogenic chemotherapy. Exposure to granisetron was maintained at a therapeutic level over the delayed-onset phase, at least 168 hours. Adverse events in both trials were as expected for granisetron; injection site reactions (eg, erythema and induration) were predominantly mild and seen in ≤20% of patients. Complete responses (no emesis, with no rescue medication) were obtained in the acute, delayed, and overall phases in ≥80% and ≥75% of patients in both trials with the 250 and 500 mg doses, respectively. After a single injection of APF530, there were dose-proportional pharmacokinetics and sustained concentrations of granisetron over 168 hours. The 250 and 500 mg doses were well tolerated and maintained therapeutic granisetron

  10. Study on the Release Rate of Niacin in Different Media for the Compound Niacin Extended-release and Simvastatin Tablets%复方辛伐他汀烟酸缓释片中烟酸在不同释放介质中的释放度研究

    Institute of Scientific and Technical Information of China (English)

    王曙光; 王林; 邵振中; 陆小平; 杭夏清

    2011-01-01

    Objective To study the release rate of niacin for Niacin extended-release and Simvastatin tablets in different media, and analyze their release behavior in vitro. Methods The release of Niacin for self~prepared and imported compound preparation in four different media were determined by UV, the kinetics model and similarity factor(f2 value) were compared. Results Self-made and imported sustained-release tablets in vitro release of nicotinic acid were complied with the Ritger-Peppas equation, the n values of the equation in the four media were from 0.45 to 0.89, indicating that the drug release was caused by the interaction of the skeleton of drug diffusion and dissolution. Comparing with the value of the reference formulation, the f2 value of the self extended-release tablets which were in water, 0.lmol/L HC1, pH 4.5 acetate buffer and pH 6.8 phosphate buffer release medium were 67.59, 80.24, 67.27 and 65.57 respectively, which were greater than 50. Conclusion Niacin release behavior of self-prepared was consistent with the imported extended-release tablets in vitro.%目的 研究辛伐他汀烟酸缓释片在不同释放介质中烟酸的释放度,分析其在体外的释放行为.方法 用UV法 测定自制与进口辛伐他汀烟酸缓释片在四种不同介质中的烟酸释放情况,并对其释放模型和f2相似因子进行比较.结果 自制和进口缓释片的烟酸体外释放度符合Ritger-Peppas方程,在四种介质中方程拟合的n值均在0.45~0.89之间,说明该药物释放是药物扩散和骨架溶蚀共同作用的.与参比制剂相比,自制缓释片在水、0.1 mol/L盐酸、pH4.5醋酸盐缓冲液及pH 6.8磷酸盐缓冲液释放介质中,f2值分别为67.59、80.24、67.27和65.57,均大于50.结论 自制制剂与进口制剂的缓释部分体外释放行为相似.

  11. Pharmacokinetics, safety, and efficacy of APF530 (extended-release granisetron in patients receiving moderately or highly emetogenic chemotherapy: results of two Phase II trials

    Directory of Open Access Journals (Sweden)

    Gabrail N

    2015-03-01

    Full Text Available Nashat Gabrail,1 Ronald Yanagihara,2 Marek Spaczyński,3 William Cooper,4 Erin O'Boyle,5 Carrie Smith,1 Ralph Boccia6 1Gabrail Cancer Center, Canton, OH, USA; 2St Louise Regional Hospital, Gilroy, CA, USA; 3Department of Gynecology, Obstetrics and Gynecologic Oncology, University of Medical Sciences, Poznan, Poland; 4TFS International, Flemington, NJ, USA; 5FibroGen, Inc., San Francisco, CA, USA; 6Center for Cancer and Blood Disorders, Bethesda, MD, USA Background: Despite advances with new therapies, a significant proportion of patients (>30% suffer delayed-onset chemotherapy-induced nausea and vomiting (CINV despite use of antiemetics. APF530 is a sustained-release subcutaneous (SC formulation of granisetron for preventing CINV. APF530 pharmacokinetics, safety, and efficacy were studied in two open-label, single-dose Phase II trials (C2005-01 and C2007-01, respectively in patients receiving moderately emetogenic chemotherapy or highly emetogenic chemotherapy. Methods: In C2005-01, 45 patients received APF530 250, 500, or 750 mg SC (granisetron 5, 10, or 15 mg, respectively. In C2007-01, 35 patients were randomized to APF530 250 or 500 mg SC. Injections were given 30 to 60 minutes before single-day moderately emetogenic chemotherapy or highly emetogenic chemotherapy. Plasma granisetron was measured from predose to 168 hours after study drug administration. Safety and efficacy were also evaluated. Results: APF530 pharmacokinetics were dose proportional, with slow absorption and elimination of granisetron after a single SC dose. Median time to maximum plasma concentration and half-life were similar for APF530 250 and 500 mg in both trials, with no differences between the groups receiving moderately and highly emetogenic chemotherapy. Exposure to granisetron was maintained at a therapeutic level over the delayed-onset phase, at least 168 hours. Adverse events in both trials were as expected for granisetron; injection site reactions (eg, erythema

  12. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial

    DEFF Research Database (Denmark)

    Diener, Hans-Christoph; Sacco, Ralph L; Yusuf, Salim

    2008-01-01

    telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. METHODS: Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER......-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed...... of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically...

  13. Trends in the consumption of attention deficit hyperactivity disorder medications in Castilla y León (Spain): changes in the consumption pattern following the introduction of extended release methylphenidate.

    Science.gov (United States)

    Treceño, Carlos; Martín Arias, Luis H; Sáinz, Maria; Salado, Inés; García Ortega, Pilar; Velasco, Veronica; Jimeno, Natalia; Escudero, Antonio; Velasco, Alfonso; Carvajal, Alfonso

    2012-04-01

    Attention deficit hyperactivity disorder (ADHD) is the most diagnosed behavioural disorder in children and adolescents; prevalence has been estimated around 5%. Studies have shown an increase in the use of ADHD medications during the last years. The aim of the present study was to learn the pattern and the evolution of ADHD medication consumption in Castilla y León (Spain). Consumption data for the period 1992-2009 were obtained from databases containing information upon consumption and cost of medications dispensed by pharmacies at the expense of the Spanish National Health System. The data were expressed in defined daily doses (DDDs) per 1000 inhabitants per day (DDD/1000 inhabitants/day). A model to forecast consumption was built. Attention deficit hyperactivity disorder medication consumption increased in Castilla y León from 0.1 DDD/1000 inhabitants/day in 1992 to 1.5 DDD/1000 inhabitants/day in 2009; expected consumption will reach 2.5 DDD/1000 inhabitants/day by 2013. The drugs accounting for this increase were mainly made up of methylphenidate preparations (1.4 DDD/1000 inhabitants/day in 2009). From 1992 to 1999, there was a slight reduction in methylphenidate use; following amphetamine withdrawal, the consumption of stimulants began to increase, and figures showed a sharp rise after marketing of extended-release formulations in 2003. There has been an enormous increase in ADHD medication consumption in Castilla y León in the last few years; increase rocketed when extended-release methylphenidate was marketed. A rapid increase in the consumption is a warning on possible overdiagnosis and inappropriate prescription. Copyright © 2012 John Wiley & Sons, Ltd.

  14. Fluvoxamina no transtorno depressivo maior: um estudo multicêntrico aberto Fluvoxamine in the treatment of major depressive disorder: an open multicentric study

    Directory of Open Access Journals (Sweden)

    José Alberto Del Porto

    2007-01-01

    Full Text Available OBJETIVO: Este trabalho estudou a eficácia e a tolerabilidade da fluvoxamina no tratamento, de forma aberta, sem comparação com placebo ou outros agentes, por 6 semanas, de pacientes com o diagnóstico de transtorno depressivo maior (TDM. Constitui-se em objetivo secundário do estudo avaliar os efeitos da fluvoxamina sobre o sono dos pacientes. MÉTODOS: Foram incluídos 104 pacientes, maiores de 18 anos, com o diagnóstico de TDM, de acordo com os critérios do Manual Diagnóstico e Estatístico de Transtornos Mentais, 4ª edição (DSM-IV, e com escores, na Escala de Hamilton para Depressão, versão de 17 itens (HAM-D 17, de 17 pontos ou mais. Avaliou-se a eficácia da fluvoxamina por meio das Escalas HAM-D 17 e da CGI (Impressão Clínica Global. A análise dos itens 4, 5 e 6 da HAM-D 17 foi utilizada para a avaliação do sono dos pacientes. Avaliaram-se a segurança e a tolerabilidade da fluvoxamina ao longo das 6 semanas, registrando-se quaisquer eventos adversos. A fluvoxamina foi inicialmente ministrada em doses de 50 ou 100 mg/dia, podendo haver aumentos progressivos até 300 mg/dia. RESULTADOS: Dos 104 pacientes incluídos, 81 (78% concluíram o estudo. Obtiveram resposta favorável (diminuição de 50% ou mais na HAM-D 17 69% dos pacientes, e a taxa de remissão (HAM-D 17 OBJECTIVE: This research studied the efficacy and tolerability of fluvoxamine in the treatment of major depressive disorder (MDD, during 6 weeks, in an open trial, without placebo or active comparator. A secondary objective was the evaluation of the effects of fluvoxamine on the sleep of the pacients. METHODS: 104 patients were inicially included, with the diagnosis of MDD in accordance to the criteria of the Diagnostic and Statistical Manual for Mental Disorders, 4th edition (DSM-IV. Patients should have scores > 17 in the Hamilton Depression Scale for Depression 17 itens (HAM-D 17. The efficacy of fluvoxamine was studied through the HAM-D 17 and CGI (Clinical

  15. Aspirin and Extended-Release Dipyridamole

    Science.gov (United States)

    ... dipyridamole is in a class of drugs called antiplatelet agents. It works by preventing excessive blood clotting. It ... Univasc), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik); anticoagulants ('blood thinners') such as warfarin (Coumadin) and heparin; ...

  16. HPLC标准曲线法测定格列吡嗪控释片的释放度及平均释放速率%DeterminationoftheDrugReleaseandtheAverageReleaseRatesofGlipizideExtendedReleaseTabletsbyHPLC StandardCurveMethod

    Institute of Scientific and Technical Information of China (English)

    窦佳; 董莉; 戴睿娇

    2013-01-01

    目的用高效液相色谱标准曲线法测定格列吡嗪控释片的释放度。方法用C18柱;流动相:磷酸盐缓冲液(取磷酸二氢钠13.8g加水溶解并稀释至1000mL,用2mol/L氢氧化钠调pH至6.0)-甲醇(55∶45);检测波长:225nm。采用标准曲线法测定释放度。结果格列吡嗪浓度在1.0~10.0μg/mL范围内与峰面积呈良好的线性关系,r=0.9998。平均加样回收率为100.19%,RSD=0.99%(n=5)。结论本方法灵敏度高、专属性强、准确可靠,较准确的反映了格列吡嗪控释片每4h的释放情况。%Objective A HPLC standard curve method has been established for the determination of the drug release of glipizide extended release tablets. Methods C18 column was used. The mobile phase was phosphate BS (dissolve 13.8g of sodium dihydrogen phosphate in water and dilute to 1000mL, adjust pH to 6.0 with 2mol•L-1 sodium hydroxide)-Methonal (55∶45). The detection wavelength was at 225 nm. The HPLC standard curve method was employed to determine the drug release. Results The linear range of 1.0~10.0μg/mL (r=0.9998) was obtained. The average recovery of add sample was 100.19%, RSD was 0.99%(n=5). Conclusion The method was of high sensitivity and speciifcity, accurate, reliable. The method can relfect accurately the drug release of glipizide extended release tablets every 4 hours.

  17. 帕利哌酮缓释片治疗酒精所致精神障碍的临床观察%Efficacy and Safety of Paliperidone Extended Release Tablets for Alcohol-induced Mental Disorder

    Institute of Scientific and Technical Information of China (English)

    马文斌

    2015-01-01

    OBJECTIVE:To evaluate the clinical efficacy and safety of paliperidone extended release tablets for alcohol-induced mental disorders.METHODS:Between Mar.2012 and July 2013, a total of 50 patients with alcohol-induced mental disorders were randomly divided into either observation group or control group, of 25 cases each.The patients in the control group were treated with haloperidol tablets for 6 weeks, while those in the observation group were treated with paliperidone extended release tablets for 6 weeks.The two groups of patients were followed with regard to clinical response, PANSS ( positive and negative syndrome scale) score, quality of life index ( QL-Index) and TESS ( treatment emergent symptom scale ) score etc.RESULTS: After treatment, the PANSS score, QL-Index and the TESS score were significantly better in the observation group than in the control group, and the differences were all statistically significant ( P<0.05);the total effective rate was significantly higher in the observation group than in the control group ( P<0.05 ) .CONCLUSIONS:Treatment of alcohol-induced mental disorders with paliperidone extended release tablets resulted in better clinical efficacy and safety than did with haloperidol tablets.%目的:探讨帕利哌酮缓释片治疗酒精所致精神障碍的临床效果与安全性。方法:将2012年3月—2013年7月50例酒精所致精神障碍患者以随机数字表法分为观察组和对照组,每组25例。对照组患者给予氟哌啶醇片,观察组患者给予帕利哌酮缓释片,均治疗6周。对比观察2组患者的临床疗效,以及阳性和阴性症状量表( positive and negative syndrome scale, PANSS)、生活质量指数(quality of life index,QL-Index)及副反应量表(treatment emergent symptom scale,TESS)等评分情况。结果:治疗后,观察组患者的PANSS、QL-Index及TESS评分均明显优于对照组,差异均有统计意义( P<0.05);观察组患者

  18. Investigation on Dissolution Characteristics of Diclofenac Sodium Extended Release Tablets Using Flow-through Cell Method%流通池法考察双氯芬酸钠缓释片的体外释放特性

    Institute of Scientific and Technical Information of China (English)

    刘曦; 王亚敏; 潘阿慧; 宁保明; 涂家生

    2013-01-01

    目的 建立统一又能够区分不同厂家来源的双氯芬酸钠(diclofenac sodium)缓释片的释放度检查方法.方法 采用流通池法,分别考察不同流速、不同介质条件下双氯芬酸钠缓释片的体外释放特性,并在最终选择的释放条件下,进行了释药曲线的相似性分析和威布尔参数的统计学分析.结果 在所选流速范围内,流速对释放度无显著影响;f2因子和威布尔参数分析结果显示流速为4 mL·min-1、流通池实验条件为0.1 mol·L-1盐酸中释放1h后更换介质为水再释放7h对于市售双氯芬酸钠缓释片样品体外释放具有良好的区分力.结论 本方法可用于实验样品的不同生产厂家的双氯芬酸钠缓释片的释放度检查,提示对于双氯芬酸钠缓释片释放度的全面考察以及仿制药质量的提高具有一定的科学实用意义.%OBJECTIVE To develop a unified and discriminative method for the characterization of different diclofenac sodium extended release tablets.METHODS The flow-through cell method was employed to investigate the dissolution characteristics of all the samples at different flow rates and in different dissolution media.The dissolution data under the finally selected dissolution condition was also used to analyze the similarity of dissolution curves and statistical significance of Weibull parameters.RESULTS The dissolution behaviors of the samples were not significantly influenced by flow rates in the selected range.The dissolution at a flow rate of 4 mL · min-1 and in hydrochloric acid (0.1 mol · L-1) for one hour followed by water for another seven hours was satisfactory to discriminate the samples,which was demonstrated by f2 and Weibull parameters analysis.CONCLUSION This method can be used for dissolution tests of diclofenac sodium extended release tablet samples from the manufacturers in this study with meanings in guiding both comprehensive investigation on the dissolution of diclofenac sodium

  19. Medication Persistence, Duration of Treatment, and Treatment-switching Patterns Among Canadian Patients Taking Once-daily Extended-release Methylphenidate Medications for Attention-Deficit/Hyperactivity Disorder: A Population-based Retrospective Cohort Study.

    Science.gov (United States)

    Park-Wyllie, Laura; Van Stralen, Judy; Almagor, Doron; Dobson-Belaire, Wendy; Charland, Katia; Smith, Andrew; Le Lorier, Jacques

    2016-08-01

    We conducted a retrospective cohort study to compare medication use patterns of a long-acting extended-release methylphenidate (Osmotic Release Oral System [OROS(®)] methylphenidate, CONCERTA(®)) and Teva-methylphenidate (methylphenidate ER-C), a generic drug determined by the Canadian regulatory authority, Health Canada, to be bioequivalent to OROS(®) methylphenidate. We established an OROS(®) methylphenidate-experienced and new-user population cohort to compare medication use patterns, including medication persistence, duration of therapy, and treatment-switching patterns. Multivariable log-binomial regression was used to adjust for confounders of the associations with persistence. In the OROS(®) methylphenidate-experienced cohort (n = 21,940), OROS(®) methylphenidate was associated with a 70% higher rate of medication persistence at 12 months relative to methylphenidate ER-C (adjusted relative risk = 1.70; 95% CI, 1.64-1.77). In the new-user cohort (n = 20,410), OROS(®) methylphenidate had a 58% higher rate of medication persistence relative to methylphenidate ER-C (adjusted relative risk = 1.58; 95% CI, 1.51-1.65). Median duration of therapy was significantly longer in patients taking OROS(®) methylphenidate compared with those taking methylphenidate ER-C, and treatment-switching occurred significantly more frequently in patients taking methylphenidate ER-C compared with those taking OROS(®) methylphenidate. Significant differences were observed in how the medications were used by patients in the real-world setting. Because the data sources were administrative databases, it was not possible to control for all potentially important confounding variables. Although differences in medication persistence may not directly reflect differences in treatment efficacy, the findings are important because these products are used interchangeably in a number of Canadian provinces. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  20. 氟伏沙明对纤维肌痛综合征的疗效与安全性观察%Observation of the efficacy and safety of Fluvoxamine in treatment of fibromyalgia syndrome

    Institute of Scientific and Technical Information of China (English)

    陈力; 徐春晖; 王燕

    2011-01-01

    目的:观察氟伏沙明治疗纤维肌痛综合征的疗效与安全性.方法:将60例门诊纤维肌痛综合征的患者,随机分为氟伏沙明组30例和安慰剂组30例.对照组治疗8周,氟伏沙明剂量50~150 mg/d,采用汉密尔顿抑郁量表(HAMD)和汉密尔顿焦虑量表(HAMA)评价疗效.结果:54例完成了8周的临床观察,治疗后两组HAMD评分均有下降,氟伏沙明组评分明显低于安慰剂组.治疗后各个时间段评定(2、4、8周)两组的差异均具有统计学意义(P<0.05).治疗8周后氟伏沙明组HAMA评分明显低于安慰剂组(6.7±4.5,11.7±8.3,P<0.01),氟伏沙明组HAMD评分明显低于安慰剂组(10.5±6.5,19.8±6.9,P<0.01).8周的治疗中氟伏沙明组仅出现轻度不良反应.结论:氟伏沙明治疗纤维肌痛综合征的疗效较好,具有良好的安全性和耐受性.%Objective: To observe the efficacy and safety of the treatment of fibromyalgia syndrome by fluvoxamine.Methods: 60 0utpatients with fibromyalgia syndrome were randomly divided into the Fluvoxamine group and placebo group, 30 cases in each group. The treatment lasted 8 weeks, evaluated by Hamilton Depression Rating Scale for Depression (HAMD) and Hamilton Anxiety Scale (HAMA). The dose of Fluvoxamine was 50~100 mg/d. Results: 54 patients completed the clinical observation of 8 weeks. After treatment, HAMD (24 items) scores of both groups decreased, and the score of the Fluvoxamine group was significantly lower than that of the placebo group. After treatment the assessments of all time (after 2, 4 weeks and 8 weeks) between the two groups had statistically significant (P<0.05). After 8 weeks, HAMA score of Fluvoxamine group was significantly lower than that of the placebo group (6.7±4.5, 11.7±8.3, P<0.01). HAMD score of fluvoxamine group was significantly lower than that of the placebo group (10.5±6.5, 19.8±6.9, P<0.01). During the treatment of 8 weeks, only mild adverse reactions were discovered in the

  1. Fluvoxamine plus cognitive behavioral therapy in the treatment of obsessivecompulsive disorder%氟伏沙明合并认知行为疗法治疗强迫症的对照研究

    Institute of Scientific and Technical Information of China (English)

    皮玥玥; 曹玉媛

    2011-01-01

    目的:探讨氟伏沙明与认知行为疗法联合治疗强迫症的疗效.方法:将48例强迫症患者分为治疗组和对照 组.每组24例.治疗组采用氟伏沙明合并认知行为治疗,对照组单用氟伏沙明治疗,疗程为3个月.分别于治疗前和 治疗后采用Yale-Brown强迫量表评定疗效,TESS评定不良反应.结果:治疗组临床有效率为79.2%(18/24),对照组 有效率为50%(12/24),两组疗效差异有统计学意义(χ2=4.46,P<0.05).结论:氟伏沙明合并认知行为治疗强迫症的 疗效明显优于单纯药物治疗.%Objective: To compare the effect of Fluvoxamine plus cognitive behavioral therapy in the treatment of obsessive-compulsive disorder. Methods: 48 patients for obsessive-compulsive disorder were assigned to therapeutic group and control group of 3 months, each group of 24 examples. Therapeutic group were given Fluvoxamine in addition to cognitive behavioral therapy, and control group were given Fluvoxamine alone. Yale-Brown scale and Tess were used to evaluate the efficacy and adverse effects respectively. Results: The effective rates of therapeutic group and control group were 79.2%and 50%, which showed significant difference between the two groups (x2=4.46, P<0.05). Conclusion: Fluvoxamine plus cognitive behavioral therapy has better effect in treatment of ohsessive-compulsive disorder.

  2. Quality measure attainment with dapagliflozin plus metformin extended-release as initial combination therapy in patients with type 2 diabetes: a post hoc pooled analysis of two clinical studies

    Science.gov (United States)

    Bell, Kelly F; Katz, Arie; Sheehan, John J

    2016-01-01

    Background The use of quality measures attempts to improve safety and health outcomes and to reduce costs. In two Phase III trials in treatment-naive patients with type 2 diabetes, dapagliflozin 5 or 10 mg/d as initial combination therapy with metformin extended-release (XR) significantly reduced glycated hemoglobin (A1C) from baseline to 24 weeks and allowed higher proportions of patients to achieve A1C LDL-C) as well as vital status measures of blood pressure (BP) and body mass index (BMI). The proportion of patients achieving A1C, BP, and LDL-C individual and composite measures was assessed, as was the proportion with baseline BMI ≥25 kg/m2 who lost ≥4.5 kg. Subgroup analyses by baseline BMI were also performed. Results A total of 194 and 211 patients were treated with dapagliflozin 5- or 10-mg/d combination therapy, respectively, and 409 with metformin monotherapy. Significantly higher proportions of patients achieved A1C ≤6.5%, LDL-C <100 mg/dL across treatment groups. A higher proportion of patients with baseline BMI ≥25 kg/m2 lost ≥4.5 kg with combination therapy. Combination therapy had a more robust effect on patients with higher baseline BMI. Conclusion Initial combination therapy with dapagliflozin 5 or 10 mg/d and metformin improved quality measures relevant to clinical outcomes and diabetes care.

  3. Pharmacokinetics of niacin extended-release/lovastatin tablets in healthy volunteers%洛伐他汀烟酸缓释片健康人体药动学研究

    Institute of Scientific and Technical Information of China (English)

    王玉; 宋敏; 杭太俊; 阙小亭; 王珵; 文爱东; 杨林

    2011-01-01

    Objective: To study the pharmacokinetics of niacin extended-release/lovastatin tablets with single and multiple oral doses in healthy Chinese volunteers. Methods: The study was carried out with an incremental dosage design after an overnight fast and light fat breakfast, and wash-out period was one week. In 12 Chinese healthy volunteers, single oral doses of niacin extended-release/lovastatin tablets (500 mg/20 mg), multiple oral doses of 500 mg/20 mg qd for 7 consecutive days, single oral doses of 750 mg/20 mg and 1 000 mg/20 mg were administered, respectively. The blood samples were taken just before and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6,8, 10, 12, 14, 24 h after the administration. The plasma concentrations of niacin (NA) , niacinamide (NAM) ,nicotinuric acid (NUR) and lovastatin were determined by validated LC-MS/MS methods, and the pharmacokinetic parameters were evaluated. Results: In the range of 500 ~ 1 000 mg of the niacin extended-release/lovastatin tablets, the AUC0-24h and Cmax of NA, NAM and NUR had good linearity with the doses after single oral administrations. No significant gender differences were found for them. The observed accumulation index values of NA, NAM and NUR after multiple oral administrations of 500 mg/20 mg niacin extended-release/lovastatin tablets were ( 8.6 ± 8.6), (3.2 ± 1.2) and (5.6 ± 3.3 ), respectively. The pharmacokinetics of lovastatin was not affected by the dosages of NA, and the accumulation index value was ( 1.6 ± 0.6) after multiple doses. Conclusion: NA and its metabolites demonstrate linear pharmacokinetics in the dose range studied. The drug accumulation after multiple oral doses is significant. No drug interaction has been found between niacin and lovastatin.%目的:研究洛伐他汀烟酸缓释片在健康人体内的药动学.方法:采用低脂早餐后剂量递增实验设计,清洗期为1周.健康受试者12名,男女各半,分别单剂量口服低剂量(烟酸500 mg/洛伐他汀20mg);连续7 d,qd

  4. Assessing the efficacy of 2 years of maintenance treatment with venlafaxine extended release 75–225 mg/day in patients with recurrent major depression: a secondary analysis of data from the PREVENT study

    Science.gov (United States)

    Kornstein, Susan G.; Kocsis, James H.; Ahmed, Saeeduddin; Thase, Michael; Friedman, Edward S.; Dunlop, Boadie W.; Yan, Bing; Pedersen, Ron; Ninan, Philip T.; Li, Thomas; Keller, Martin

    2013-01-01

    The objective of this study was to evaluate the long-term efficacy of venlafaxine extended release (ER) ≤225 mg/ day in patients with recurrent major depressive disorder (MDD). In this double-blind trial, outpatients with recurrent MDD (N=1096) were randomized to 10 weeks of acute-phase treatment with venlafaxine ER (75–300 mg/ day) or fluoxetine (20–60 mg/day) followed by a 6-month continuation phase and two consecutive 12-month maintenance phases. At the start of each maintenance period, venlafaxine ER responders were randomized to double-blind venlafaxine ER or placebo. In this analysis, data from responders to acute and continuation treatment were analyzed during the combined maintenance phases while receiving venlafaxine ER ≤225 mg/day. Failure to maintain response was defined as an increase in maintenance dose to 300 mg/day or recurrence. Differences were calculated using Kaplan–Meier methods and compared using log-rank tests. Continuation-phase responders (n =114) receiving venlafaxine ER ≤225 mg/ day comprised the analysis population (venlafaxine ER: n= 55; placebo: n= 59). The estimated probability for remaining well across 24 months of maintenance treatment was 67% for venlafaxine ER and 41% for placebo (P = 0.007). Venlafaxine ER effectively maintained response at doses ≤225 mg/day for up to 2.5 years in patients with recurrent MDD. The findings are consistent with those of the full data set. PMID:18854724

  5. Efficacy of extended release quetiapine fumarate monotherapy in elderly patients with major depressive disorder: secondary analyses in subgroups of patients according to baseline anxiety, sleep disturbance, and pain levels.

    Science.gov (United States)

    Montgomery, Stuart A; Altamura, A Carlo; Katila, Heikki; Datto, Catherine; Szamosi, Johan; Eriksson, Hans

    2014-03-01

    This study evaluated extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder (MDD) according to baseline levels of anxiety, sleep disturbance, and pain. Post-hoc analyses of data from an 11-week (9-week randomized-treatment, 2-week post-treatment phase), double-blind, placebo-controlled study of quetiapine XR (50-300 mg/day) monotherapy in elderly (≥66 years) patients (n=338) with MDD were carried out. Outcomes included randomization to week 9 change in Montgomery Åsberg Depression Rating Scale (MADRS) score and week 9 response (≥50% MADRS score reduction) rates. Post-hoc analyses were carried out to assess subgroups of patients with MDD according to baseline levels in terms of the following: higher or lower anxiety (Hamilton Rating Scale for Anxiety total score≥20 or Depression sleep disturbance factor (items 4+5+6) score≥5 or depressive symptoms in elderly patients with MDD, irrespective of baseline levels of anxiety, sleep disturbance, and pain.

  6. Extended Emotions

    DEFF Research Database (Denmark)

    Krueger, Joel; Szanto, Thomas

    2016-01-01

    Until recently, philosophers and psychologists conceived of emotions as brain- and body-bound affairs. But researchers have started to challenge this internalist and individualist orthodoxy. A rapidly growing body of work suggests that some emotions incorporate external resources and thus extend...... beyond the neurophysiological confines of organisms; some even argue that emotions can be socially extended and shared by multiple agents. Call this the extended emotions thesis (ExE). In this article, we consider different ways of understanding ExE in philosophy, psychology, and the cognitive sciences....... First, we outline the background of the debate and discuss different argumentative strategies for ExE. In particular, we distinguish ExE from cognate but more moderate claims about the embodied and situated nature of cognition and emotion (Section 1). We then dwell upon two dimensions of ExE: emotions...

  7. Extended thermodynamics

    CERN Document Server

    Müller, Ingo

    1993-01-01

    Physicists firmly believe that the differential equations of nature should be hyperbolic so as to exclude action at a distance; yet the equations of irreversible thermodynamics - those of Navier-Stokes and Fourier - are parabolic. This incompatibility between the expectation of physicists and the classical laws of thermodynamics has prompted the formulation of extended thermodynamics. After describing the motifs and early evolution of this new branch of irreversible thermodynamics, the authors apply the theory to mon-atomic gases, mixtures of gases, relativistic gases, and "gases" of phonons and photons. The discussion brings into perspective the various phenomena called second sound, such as heat propagation, propagation of shear stress and concentration, and the second sound in liquid helium. The formal mathematical structure of extended thermodynamics is exposed and the theory is shown to be fully compatible with the kinetic theory of gases. The study closes with the testing of extended thermodynamics thro...

  8. Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline.

    Science.gov (United States)

    Waldinger, M D; Hengeveld, M W; Zwinderman, A H; Olivier, B

    1998-08-01

    Depression is a common cause of sexual dysfunction, but also antidepressant medication is often associated with sexual side effects. This article includes two related studies. The first double-blind, placebo-controlled study was conducted in men with lifelong rapid ejaculation and aimed to assess putative differences between the major selective serotonin reuptake inhibitors (SSRIs) (fluoxetine, fluvoxamine, paroxetine, and sertraline) with regard to their ejaculation-delaying effect. Sixty men with an intravaginal ejaculation latency time (IELT) of 1 minute or less were randomly assigned to receive fluoxetine 20 mg/day, fluvoxamine 100 mg/day, paroxetine 20 mg/day, sertraline 50 mg/day, or placebo for 6 weeks. During the 1-month baseline and 6-week treatment periods, the men measured their IELT at home using a stopwatch. The trial was completed by 51 men. During the 6-week treatment period, the geometric mean IELT in the placebo group was constant at approximately 20 seconds. Analysis of variance revealed a between-groups difference in the evolution of IELT delay (p = 0.0004); in the paroxetine, fluoxetine, and sertraline groups there was a gradual increase to about 110 seconds, whereas in the fluvoxamine group, IELT was increased to only approximately 40 seconds. The paroxetine, fluoxetine, and sertraline groups differed significantly (p IELT IELT > 1 minute) to investigate whether data about SSRI-induced delayed ejaculation in men with rapid ejaculation may be extrapolated to men with less-rapid ejaculation. After measurement of IELT at home (using a stopwatch) during a 1-month baseline assessment, 32 men with an IELT of 1 minute or less (group 1) or more than 1 minute (group 2) were randomly assigned to receive paroxetine 20 mg/day or placebo for 6 weeks in a double-blind manner. Patients continued to measure their IELTs at home during the 6 weeks of the study. At baseline, 24 patients consistently had IELTs of one minute or less (group 1), and eight patients

  9. Single-dose extended-release oral azithromycin vs. 3-day azithromycin for the treatment of group A beta-haemolytic streptococcal pharyngitis/tonsillitis in adults and adolescents: a double-blind, double-dummy study.

    Science.gov (United States)

    Jorgensen, D M

    2009-12-01

    The azithromycin immediate-release formulation (AZ-IR) provides effective treatment for group A beta-haemolytic streptococcal pharyngitis in adults. Single-dose therapy with a novel azithromycin extended-release (AZ-ER) formulation could reduce treatment failure and eliminate non-compliance contributing to antimicrobial resistance. A randomized, double-blind, double-dummy, multicentre trial was conducted comparing AZ-ER (single oral 2-g dose) with AZ-IR (3 days, 500 mg once daily) for the treatment of group A beta-haemolytic streptococcal pharyngitis/tonsillitis in adults and adolescents (n = 598). The primary endpoint was bacteriological eradication at test -of-cure (TOC; day 24-28) in the bacteriological per-protocol population (n = 420). Bacteriological eradication was achieved in 85.4% (175/205) and 81.4% (175/215) of subjects in the AZ-ER and AZ-IR groups, respectively (95% CI -3.1-11.1). Clinical cure at TOC occurred in 99.0% of subjects in the AZ-ER group and in 96.7% in the AZ-IR group. At long-term follow-up, bacteriological recurrence was observed in 5.5% (9/163) and 7.7% (12/156), respectively. Both treatments were well tolerated; and most adverse events (AEs) were mild to moderate in intensity. The most frequent treatment-related AE was diarrhoea, or loose stools, in 11% of both treatment groups. AZ-ER-treated and AZ-IR-treated subjects had AE burdens (AE days/patient-year) of 7.6 days and 9.2 days, respectively. A similar trend in favour of AZ-ER was noted for treatment-related diarrhoea burden (1.9 days vs. 2.5 days). A single 2-g dose of AZ-ER is as effective and well tolerated as 3 days of AZ-IR (500 mg once daily) for treating group A beta-haemolytic streptococcal pharyngitis/tonsillitis in adults and adolescents.

  10. Efficacy and tolerability of a hydrocodone extended-release tablet formulated with abuse-deterrence technology for the treatment of moderate-to-severe chronic pain in patients with osteoarthritis or low back pain

    Directory of Open Access Journals (Sweden)

    Hale ME

    2015-09-01

    Full Text Available Martin E Hale,1 Charles Laudadio,2 Ronghua Yang,2 Arvind Narayana,2 Richard Malamut2 1Gold Coast Research, LLC, Plantation, FL, 2Teva Branded Pharmaceutical Products R & D, Inc., Frazer, PA, USA Abstract: This double-blind, placebo-controlled study evaluated the efficacy and safety of hydrocodone extended release (ER developed with abuse-deterrence technology to provide sustained pain relief and limit effects of alcohol and tablet manipulation on drug release. Eligible patients with chronic moderate-to-severe low back or osteoarthritis pain were titrated to an analgesic dose of hydrocodone ER (15–90 mg and randomized to placebo or hydrocodone ER every 12 hours. The primary efficacy measure was change from baseline to week 12 in weekly average pain intensity (API; 0=no pain, 10=worst pain imaginable. Secondary measures included percentage of patients with >33% and >50% increases from baseline in weekly API, change from baseline in weekly worst pain intensity, supplemental opioid usage, aberrant drug-use behaviors, and adverse events. Overall, 294 patients were randomized and received ≥1 dose of placebo (n=148 or hydrocodone ER (n=146. Weekly API did not differ significantly between hydrocodone ER and placebo at week 12 (P=0.134; although, in post hoc analyses, the change in weekly API was significantly lower with hydrocodone ER when excluding the lowest dose (15 mg; least squares mean, –0.20 vs 0.40; P=0.032. Significantly more patients had .33% and .50% increase in weekly API with placebo (P<0.05, and mean weekly worst pain intensity was significantly lower with hydrocodone ER at week 12 (P=0.026. Supplemental medication usage was higher with placebo (86% than hydrocodone ER (79%. Incidence of aberrant drug-use behaviors was low, and adverse events were similar between groups. This study did not meet the primary endpoint, although results support the effectiveness of this hydrocodone ER formulation in managing chronic low back or

  11. A pharmacokinetic comparison of single doses of once-daily cyclobenzaprine extended-release 15 mg and 30 mg: a randomized, double-blind, two-period crossover study in healthy volunteers.

    Science.gov (United States)

    Darwish, Mona; Chang, Steven; Hellriegel, Edward T

    2009-01-01

    The purpose of this study was to compare the pharmacokinetics and tolerability of single oral doses of cyclobenzaprine extended-release (CER) 15- and 30-mg capsules. This was a randomized, double-blind, 2-period crossover study in healthy adults aged 18 to 40 years. Subjects were assigned to receive a single dose of either CER 15 mg or 30 mg on days 1 and 15, separated by a 14-day washout. Study comparisons included the plasma cyclobenzaprine AUC to 168 hours after dosing (AUC(0-168)), AUC(0-infinity), and C(max). Plasma cyclobenzaprine T(max), terminal elimination t(1/2), and adverse events (AEs) were also assessed. Sixteen subjects (9 women, 7 men) were randomized to receive cyclobenzaprine 15 mg or 30 mg; 13 (81.3%) were white and 3 (18.8%) were black. Mean age and weight were 30.2 years and 70.7 kg, respectively. The shapes of the pharmacokinetic profiles for CER 15 and 30 mg were parallel. Mean observed values for dose-dependent pharmacokinetic parameters of CER 15 and 30 mg were as follows: AUC(0-168), 318.3 and 736.6 ng . h/mL, respectively; AUC(0-infinity)), 354.1 and 779.9 ng . h/mL; and C(max), 8.3 and 19.9 ng/mL. Dose-independent parameters were comparable across doses. Median observed Tmax was 6.0 hours for both CER doses; mean t(1/2) was 33.4 hours for CER 15 mg and 32.0 hours for CER 30 mg. The bioavailability of the 2 doses, as indicated by the least squares mean AUC(0-infinity), was 330.3 ng . h/mL for CER 15 mg and 755.1 ng . h/mL for CER 30 mg. During the CER 15-mg treatment sequence, 5 subjects experienced 5 AEs (headache, dizziness, musculoskeletal pain, dermatitis, and glossodynia); during the CER 30-mg treatment sequence, 2 subjects experienced 2 AEs (somnolence and dysmenorrhea). All AEs were mild in intensity. No serious AEs occurred during the study. Once-daily CER 15 and 30 mg exhibited similarly shaped pharmacokinetic profiles. AUC(0-168), AUC(0-infinity)), and C(max) values for the 30-mg dose were approximately double those for the 15-mg

  12. 烟酸/辛伐他丁缓释片乙醇残留的GC测定%Determination of residual ethanol in Niacin Extended-Release/Simvastatin Tablets by capilary GC

    Institute of Scientific and Technical Information of China (English)

    张嘉颖(通讯作者); 池舒耀; 叶汝汉; 彭蕾; 孙晋红

    2013-01-01

      Objective: To develop a GC method for determination the content of residual solvent ethanol in Niacin Extended-Release/Simvastatin Tablets. Methods: With Analytical Technology AT.SE-54 capilary column (30 m×0.32 mm, 1.0 μm), FID detector, the samples were dissolved in water, and were sampled with a headspace sampler. The GC oven temperature was kept at 40° C for 5 minutes, and then was increased to 110° C at a 20℃ /min speed, and then was kept at 110℃ for 1 min. The injection port and detector temperatures were 200℃ and 250℃ re•spectively. The split ratio was 10:1. Nitrogen was used as carrier gas. Results: Under these chromatographic conditions, ethanol and internal standard were completely separated. The calibration curve of ethanol was linear in the range of 5.9-177.2 μg/ml (r=0.999). The average re•covery of ethanol at three concentrations (5%, 100%和150%) were 95.5%,107.1%,109.5%, with RSD of 3.1%,0.6%,1.3% respectively. The absolute difference of ethanol content results between the repeatability solutions and the intermediate precision solutions was zero. The limit of detection (LOD) of this method for ethanol was 0.738μg /ml and limit of quantitation (LOQ) of this method for ethanol was 0.236μg /ml. Conclusion: The method is rapid, sensitive, and precise with good reproducibility. It is suitable for the determination of residual ethanol in Niacin Extended-Release/Simvastatin Tablets.%  目的:建立烟酸/辛伐他丁缓释片有机溶剂乙醇残留量的测定方法。方法:采用毛细管气相色谱法,顶空进样,氢火焰离子化检测器(FID),以水为溶剂,色谱柱为 Analytical Technology AT.SE-54(30 m×0.32 mm,1.0μm),分流比10:1,进样口温度200℃,检测器温度250℃,柱温40℃,保持5分钟,然后以20℃/分钟升温速度升到110℃,保持1分钟,载气为氮气。结果:在该色谱条件下乙醇与内标能达到完全分离,测得乙醇在5.9-177.2μg

  13. Extended-Release Guaifenesin/Pseudoephedrine Hydrochloride for Symptom Relief in Support of a Wait-and-See Approach for the Treatment of Acute Upper Respiratory Tract Infections: A Randomized, Double-Blind, Placebo-Controlled Study.

    Science.gov (United States)

    Septimus, Edward J; Albrecht, Helmut H; Solomon, Gail; Shea, Tim; Guenin, Eric P

    2017-01-01

    Despite the well-known fact that antibiotics (AB) are not effective against viruses, many patients ask for - and all too often doctors provide - AB for treating URTIs. Over-prescribing of AB is one of the key causes for the development of bacterial resistance, which the U.S. Centers for Disease Control and Prevention (CDC) calls "one of the world's most pressing public health problems". In addition to the CDC initiated "Get Smart About Antibiotics" campaign, focused on educating doctors the public about the importance of appropriate AB use, other programs tackling this problem include the development of new treatment paradigms. Data published at the Oregon Health & Science University demonstrated that a 'wait-and-see' approach, without an AB prescription for the treatment of acute childhood ear infections, was as quick, safe, and effective in resolving the infections as an AB prescription (Spiro DM, Tay KY, Arnold DH, Dziura JD, Baker MD, Shapiro ED. Wait-and-See Prescription for the Treatment of Acute Otitis Media. JAMA 2006; 296:1235-1241). To try and reduce inappropriate prescribing practices, a wait and see or delayed approach requires patients to return for a prescription if their symptoms persist or worsen. The aim of this study was to determine whether treatment with Mucinex D (Reckitt Benckiser LLC, Parsippany, New Jersey) lowers the use of antibiotics in the treatment of URTIs when compared with placebo. Patients aged 18 to 75 years with symptoms of acute URTIs were randomized to 1200 mg guaifenesin/120 mg pseudoephedrine hydrochloride extended-release, bilayer tablets or matching placebo for 7 consecutive days. Eligible patients met physician's criteria for antibiotic therapy but were considered suitable for a wait and see approach (withholding antibiotics for ≥48 hours). Patients recorded symptom ratings via an interactive voice response system. One thousand one hundred eighty-nine patients enrolled; data are presented for the modified intent

  14. 非洛地平缓释片在中国健康男性的生物等效性%Bioequivalence of felodipine extended release tablets in Chinese healthy male subjects

    Institute of Scientific and Technical Information of China (English)

    许俊羽; 赵侠; 孙严彤; 顾景凯; 王梓凝; 张冬梅; 周颖; 梁雁; 崔一民

    2013-01-01

    目的 评价2种非洛地平缓释片在健康中国男性人体的生物等效性.方法 用双交叉设计,24名健康男性受试者随机分为2组,单剂量口服非洛地平缓释片试验药物或对照药物5mg,用液相色谱-串联质谱法测定血浆非洛地平血药浓度,用DAS 2.0软件计算药代动力学参数.结果 试验药物与对照药物的Cmax分别为(2.15±1.37),(1.67±0.87) ng·mL-1;Tmax分别为(5.40±3.42),(5.85±4.84)h;t1/2分别为(16.51±5.82),(18.78±8.16)h;AUCo-72h分别为(37.68±22.05),(34.71±20.88)ng·h·mL-1;AUCo-∞分别为(39.90±23.64),(37.93±23.75)ng·h·mL-1;Cmax、AUCo-r2h和AUCo-∞的90%可信区间分别为109.6% ~ 141.6%,99.2% ~120.2%和96.2% ~117.8%.两制剂的Tmax非参数法检验差异无统计学意义.试验药物对于对照药物的平均相对生物利用度F为(114.0±33.7)%.结论 2种非洛地平缓释片剂在中国健康男性受试者体内具有生物等效性.%Objective To evaluate the bioequivalence of the two felo-dipine extended release tablets in Chinese healthy male subjects. Methods A single oral dose 5 mg of test and reference felodipine extended release tablets were given to 24 subjects according to an open randomized crossover design. The concentrations of felodipine in plasma were determined by LC - MS/MS. The pharmacokinetic parameters were calculated and the bioequivalence was compared by DAS 2. 0. Results The main pharmacokinetic parameters of felodipine of the test and reference preparations were as follows:Cmax were (2. 15 ± 1. 37) and (1. 67 ±0. 87) ng · mL-1; Tmax were (5. 40 ±3.42), (5. 85 ±4. 84) h; t1/2 were (16. 51 ±5.82) and (18.78 ±8. 16) h; AUC0-72hwere (37.68 ±22.05) and (34.71 ±20.88) ng · H · mL-1; AUC0_. Were (39. 90 ± 23. 64) and (37. 93 ±23. 75) ng · H · mL-1. The 90% confidential interval of Cmax, AUC0-72h and AUC0_∞ of tested formulation were 109. 6% ~ 141. 6% , 99. 2% ~ 120. 2 % and 96. 2% ~ 117. 8% . There was no

  15. Extending Puppet

    CERN Document Server

    Franceschi, Alessandro

    2014-01-01

    This book is a clear, detailed and practical guide to learn about designing and deploying you puppet architecture, with informative examples to highlight and explain concepts in a focused manner. This book is designed for users who already have good experience with Puppet, and will surprise experienced users with innovative topics that explore how to design, implement, adapt, and deploy a Puppet architecture. The key to extending Puppet is the development of types and providers, for which you must be familiar with Ruby.

  16. Efficacy, Safety, and Tolerability of an Extended-Release Orally Disintegrating Methylphenidate Tablet in Children 6–12 Years of Age with Attention-Deficit/Hyperactivity Disorder in the Laboratory Classroom Setting

    Science.gov (United States)

    Childress, Ann C.; Kollins, Scott H.; Cutler, Andrew J.; Marraffino, Andrea; Sikes, Carolyn R.

    2017-01-01

    Abstract Objective: Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) represent a new technology for MPH delivery. ODTs disintegrate in the mouth without water and provide a pharmacokinetic profile that is consistent with once-daily dosing. This study sought to determine the efficacy, safety, and tolerability of this novel MPH XR-ODT formulation in school-age children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. Methods: Children aged 6–12 years with ADHD (n = 87) were enrolled in this randomized, multicenter, double-blind, placebo-controlled, parallel, laboratory classroom study. The MPH XR-ODT dose was titrated to an optimized dose during a 4-week open-label period and maintained on that dose for 1 week. Participants (n = 85) were then randomized to receive their optimized dose of MPH XR-ODT or placebo once daily for 1 week (double blind), culminating in a laboratory classroom testing day. Efficacy was evaluated using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Attention, Deportment, and Combined scores along with Permanent Product Measure of Performance (PERMP; Attempted and Correct) assessments. Onset and duration of drug action were also evaluated as key secondary endpoints. Safety assessments included adverse events (AEs), physical examinations, electrocardiograms (ECGs), and the Columbia Suicide Severity Rating Scale (C-SSRS). Results: The average SKAMP-Combined score on the classroom study day was significantly better for the MPH XR-ODT group (n = 43) than for the placebo group (n = 39; p headache, insomnia, upper respiratory tract infection, affect lability, irritability, cough, and vomiting. Conclusions: MPH XR-ODT was effective and well tolerated for the treatment of children with ADHD in a laboratory classroom setting. Clinical Trial Registry: NCT01835548 (ClinicalTrials.gov). PMID:27183299

  17. A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.

    Science.gov (United States)

    Rauck, Richard L; Hale, Martin E; Bass, Almasa; Bramson, Candace; Pixton, Glenn; Wilson, Jacquelyn G; Setnik, Beatrice; Meisner, Paul; Sommerville, Kenneth W; Malhotra, Bimal K; Wolfram, Gernot

    2015-09-01

    The objective of this multicenter, double-blind, placebo-controlled, randomized withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse-deterrent formulation containing pellets of extended-release oxycodone hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo in the treatment of moderate-to-severe chronic low back pain. An open-label titration period in which all patients received ALO-02 was followed by a double-blind treatment period where patients meeting treatment response criteria were randomized to either a fixed dose of ALO-02 or placebo. Daily average low back pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663 patients screened, 410 received ALO-02 during the open-label conversion and titration period and 281 patients were randomized to the double-blind treatment period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score from randomization baseline to the final 2 weeks of the treatment period was significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty-four percent of patients treated with placebo and 57.5% of patients treated with ALO-02 reported ≥30% improvement in weekly average NRS-Pain scores from screening to the final 2 weeks of the treatment period (P = 0.0248). In the double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of patients in the placebo group experienced a treatment-emergent adverse event (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment period were nausea, vomiting, and constipation, consistent with opioid therapy. ALO-02 has been demonstrated to provide significant reduction of pain in patients with chronic low back pain and has a safety profile similar to other opioids.

  18. Efficacy, Safety, and Tolerability of an Extended-Release Orally Disintegrating Methylphenidate Tablet in Children 6-12 Years of Age with Attention-Deficit/Hyperactivity Disorder in the Laboratory Classroom Setting.

    Science.gov (United States)

    Childress, Ann C; Kollins, Scott H; Cutler, Andrew J; Marraffino, Andrea; Sikes, Carolyn R

    2017-02-01

    Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) represent a new technology for MPH delivery. ODTs disintegrate in the mouth without water and provide a pharmacokinetic profile that is consistent with once-daily dosing. This study sought to determine the efficacy, safety, and tolerability of this novel MPH XR-ODT formulation in school-age children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. Children aged 6-12 years with ADHD (n = 87) were enrolled in this randomized, multicenter, double-blind, placebo-controlled, parallel, laboratory classroom study. The MPH XR-ODT dose was titrated to an optimized dose during a 4-week open-label period and maintained on that dose for 1 week. Participants (n = 85) were then randomized to receive their optimized dose of MPH XR-ODT or placebo once daily for 1 week (double blind), culminating in a laboratory classroom testing day. Efficacy was evaluated using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Attention, Deportment, and Combined scores along with Permanent Product Measure of Performance (PERMP; Attempted and Correct) assessments. Onset and duration of drug action were also evaluated as key secondary endpoints. Safety assessments included adverse events (AEs), physical examinations, electrocardiograms (ECGs), and the Columbia Suicide Severity Rating Scale (C-SSRS). The average SKAMP-Combined score on the classroom study day was significantly better for the MPH XR-ODT group (n = 43) than for the placebo group (n = 39; p classroom setting. Clinical Trial Registry: NCT01835548 ( ClinicalTrials.gov ).

  19. A randomized, double-blind, parallel-group, multicenter, placebo-controlled study of the safety and efficacy of extended-release guaifenesin/pseudoephedrine hydrochloride for symptom relief as an adjunctive therapy to antibiotic treatment of acute respiratory infections.

    Science.gov (United States)

    LaForce, Craig; Gentile, Deborah A; Skoner, David P

    2008-07-01

    This study assessed the efficacy and safety of guaifenesin 600 mg and pseudoephedrine hydrochloride 60 mg extended-release bilayer tablets in providing relief of acute respiratory symptoms when used as an adjunct to antibiotics in patients with an acute respiratory infection (ARI). Adult patients experiencing symptoms of ARI and meeting the physician's usual diagnostic criteria for oral antibiotic treatment were prescribed an antibiotic and randomized to adjunctive guaifenesin/pseudoephedrine hydrochloride or matching placebo twice daily for 7 days. Patients completed symptom diaries and treatment assessments twice daily and attended office visits on Days 4 and 8. The safety/intent-to-treat (ITT) population analysis included 601 patients (guaifenesin/pseudoephedrine, n = 303; placebo, n = 298). Mean symptom scores were lower with guaifenesin/pseudoephedrine from Day 3 for every symptom assessed, with statistically significant improvements in total symptom score from Day 3 (P = 0.026). The greatest effects of treatment with guaifenesin/pseudoephedrine were observed for nasal congestion and sinus headache. Time to overall relief was shorter with guaifenesin/pseudoephedrine (P = 0.038). Significantly more patients reported "the medication was helping during the day" on Day 2 with guaifenesin/pseudoephedrine (P = 0.002). Patient assessments of symptom relief showed a significant preference for guaifenesin/pseudoephedrine versus placebo (P = 0.021). Treatment with guaifenesin/pseudoephedrine was well tolerated. Insomnia (2.6%), nausea (2.3%), and headache (1.3%) were the most common treatment-related adverse effects. As adjunctive therapy for symptom relief for patients taking antibiotics for ARIs, guaifenesin/pseudoephedrine shortened time to relief and improved bothersome respiratory symptoms better than placebo, with greatest effects seen for nasal congestion and sinus headache.

  20. Evaluation of Quality of Life, Functioning, Disability, and Work/School Productivity Following Treatment with an Extended-Release Hydrocodone Tablet Formulated with Abuse-Deterrence Technology: A 12-month Open-label Study in Patients with Chronic Pain.

    Science.gov (United States)

    Hale, Martin E; Zimmerman, Thomas R; Ma, Yuju; Malamut, Richard

    2017-02-01

    This phase 3 study evaluated quality of life, functioning, and productivity after treatment with extended-release (ER) hydrocodone formulated with CIMA(®) Abuse-Deterrence Technology platform. Patients with chronic pain were rolled over from a 12-week placebo-controlled hydrocodone ER study or were newly enrolled. Hydrocodone ER doses were titrated (15 to 90 mg every 12 hours) to an analgesic dose, and patients received up to 52 weeks of open-label treatment. Assessments included Clinician Assessment of Patient Function (CAPF), Patient Assessment of Function (PAF), Brief Pain Inventory-Short Form (BPI-SF), 36-item Short-Form Health Survey (SF-36), Sheehan Disability Scale (SDS), and World Health Organization Health and Work Performance Questionnaire-Short Form (HPQ-SF). Of 330 enrolled patients, 291 composed the full analysis population. By week 4, ≥ 50% of patients showed improvement from baseline in all 5 CAPF domains (general activities, walking, work/daily living, relationships, and enjoyment of life) and 6 of 7 PAF domains (work attendance, work performance, walking, exercise, socializing, and enjoying life). Mean decreases from baseline of 2 to 3 points were noted for BPI-SF pain interference questions from week 4 through endpoint. Mean improvements from baseline to endpoint in SF-36 subscales ranged from 3.3 to 22.3, and SDS scores improved from moderate (4.8 to 5.1) to mild (2.5 to 2.8) disruptions in work/school, social life, and family life. At endpoint, mean HPQ-SF absolute absenteeism scores decreased from 13.6 to 10.0 hours lost/month and absolute presenteeism scores improved from 67.0 to 77.1. Patients receiving hydrocodone ER showed early numeric improvements in functioning that continued throughout this 12-month study. © 2016 World Institute of Pain.

  1. The safety and effectiveness of open-label extended-release carbamazepine in the treatment of children and adolescents with bipolar I disorder suffering from a manic or mixed episode.

    Science.gov (United States)

    Findling, Robert L; Ginsberg, Lawrence D

    2014-01-01

    To assess the safety and effectiveness of open-label treatment with extended-release carbamazepine (ERC) in pediatric subjects suffering from bipolar I disorder. Medically healthy youths aged 10-17 years suffering from an acute manic or mixed episode were eligible. After screening for study eligibility, the youths began a 5-week titration period in which doses of ERC were adjusted in order to optimize benefit whilst minimizing adverse events, at doses between 200-1,200 mg/day. Thereafter, subjects could continue to receive treatment during a subsequent 21-week period. Safety measures included spontaneously reported adverse events (AEs) and laboratory assessments. The primary efficacy measure was the Young Mania Rating Scale (YMRS). A total of 60 children (ages 10-12) and 97 adolescents (ages 13-17), with an overall average age of 13.4 years (standard deviation [SD] 2.0 years) received ERC. The mean duration of study participation was 109.6 days (SD 70.2 days), with 66 (42%) completing the entire study. At end of study participation (end point), the most prevalent dose of ERC was 1,200 mg: 31.7% of children and 24.7% of adolescents reached the 1,200 mg dose. The YMRS decreased from a mean of 28.6 (SD 6.2) at baseline to a mean of 13.8 (SD 9.4) (P<0.0001) at end point. A total of 26 subjects discontinued study participation because of AEs, the most common of which were rash (n=6), white blood cell count decreased (n=5), nausea (n=3), and vomiting (n=3). No deaths were reported. The most commonly reported AEs were headache (n=41), somnolence (n=30), nausea (n=22), dizziness (n=21), and fatigue (n=19). Open-label administration of ERC might be a safe and effective intervention in this subject population. More definitive studies are warranted.

  2. Lanreotide extended-release aqueous-gel formulation, injected by patient, partner or healthcare provider in patients with acromegaly in the United States: 1-year data from the SODA registry.

    Science.gov (United States)

    Salvatori, Roberto; Woodmansee, Whitney W; Molitch, Mark; Gordon, Murray B; Lomax, Kathleen G

    2014-02-01

    Lanreotide depot (LD; commercial name Somatuline(®) Depot) is an injectable, extended-release formulation of the synthetic somatostatin analog (SSA) lanreotide. In recent clinical trials, LD was found to be suitable for self or partner administration, avoiding the need to travel to a medical facility. The Somatuline(®) Depot for Acromegaly (SODA) study is an ongoing, multicenter, observational study in the US investigating the efficacy, safety, convenience and symptom relief provided by LD in patients with acromegaly. Sub-analyses explore outcomes according to who administered the injection: patient, partner, healthcare provider (HCP) or a combination. Data reported here reflect one year of patient experience. Patients are eligible for inclusion if they have a diagnosis of acromegaly, are treated with LD and can give signed informed consent. Baseline data include patient demographics, previous acromegaly treatment and investigations, GH and IGF-I levels, LD dose and dose adjustment frequency. Symptom frequency, injection pain and treatment convenience are assessed using patient-reported questionnaires. As of 18 April 2012, 166 patients had enrolled in SODA. Most (72 %) achieved normal IGF-I levels after 12 months of LD treatment. Disease control was similar in self or partner injectors and in patients who received injections from their HCP, although self or partner injecting was deemed more convenient. LD was well-tolerated irrespective of who performed the injection. Self injection led to more injection-site reactions, but this did not increase the rate of treatment interruption. Acromegaly symptoms remained stable. Biochemical, safety and convenience data support the clinical validity of injecting LD at home.

  3. Study on Pharmacokinetics of Cetirizine/Pseudoephedrine Extended - Release Tablet in Chinese Volunteers%西替伪麻缓释片在中国志愿者体内的药代动力学研究

    Institute of Scientific and Technical Information of China (English)

    胡岳江; 张志涛; 蒋志文

    2011-01-01

    Objective To study the pharmacokinetics of Cetirizine/Pseudoephedrine Extended - Release Tabiet in Chinese volunteers. Methods Tweenty - four healthy volunteers were divided into 2 groups to receive orally a single dose of Cetirizine/Pseudoephedrine Extended - Release Tablet 1 or 2 pills respectively. Then 12 volunteers of the total each received 2 tablets per day for 5 consecutive days. The concentrations of cetirizine and pseudoephedrine in human plasma were determined simultaneously by LC - MS/MS method. Results The main pharmacokinetic parameters of cetirizine of 2 groups after single -dose were as follows: Cmax were (134. 5 ±22. 0)μg/L and (290. 9±47.4) μg/L; AUC0 -36 h were (1 369. 3±314. 9) μg · h/L and (2 403. 0±304. 9) μg · h/L, respectively. The main pharmacokinetic parameters of pseudoephedrine were as follows: Cmax were (434. 2 ±95. 0) μg/L and (932. 5 ±280. 8) μg/L; AUC0-36 h were (6 160. 7 ±1 477. 4) and (12 871.4± 4 863. 2)μg · h/L, respectively. The main pharmacokinetic parameters of cetirizine and pseudoephedrine after multi - doses were as follows: Cav were (135. 6 ±23. 4) μg/L and (417. 9 ± 126. 0) μg/L; Tmax were (0. 9 ±0. 5)h and (4. 1 ± 1. 7) h; AUss were (1 626. 7±280. 8) μg ·h/L and (5 015. 0 ± 1511. 8) μg · h/L; DF were 1. 3 ±0. 2 and 0. 7±0. 2, R were 1. 3 ± 0. 1 and 1. 2±0. 1 ,respectively. Conclusion The method was proved to be rapid, sensitive, accurate and convenient. There were no accumulations in vivo after multiple oral doses. Pseudoephedrine had extended - release character from the test tablet.%目的 研究中国健康志愿者口服西替伪麻缓释片的药动学过程.方法 将24名志愿者随机均分为高剂量组和中剂量组,分别单次口服西替伪麻缓释片1片和2片;单次给药结束1周后,中剂量组12名受试者连续5 d每天口服2片,采用液相色谱-串联质谱法同时测定人血浆中西替利嗪和伪麻黄碱的质量浓度.结果 西替利嗪单次给药

  4. Extending Experiences

    DEFF Research Database (Denmark)

    A computer game's player is experiencing not only the game as a designer-made artefact, but also a multitude of social and cultural practices and contexts of both computer game play and everyday life. As a truly multidisciplinary anthology, Extending Experiences sheds new light on the mesh...... of possibilities and influences the player engages with. Part one, Experiential Structures of Play, considers some of the key concepts commonly used to address the experience of a computer game player. The second part, Bordering Play, discusses conceptual and practical overlaps of games and everyday life...

  5. Consciousness extended

    DEFF Research Database (Denmark)

    Carrara-Augustenborg, Claudia

    2012-01-01

    There is no consensus yet regarding a conceptualization of consciousness able to accommodate all the features of such complex phenomenon. Different theoretical and empirical models lend strength to both the occurrence of a non-accessible informational broadcast, and to the mobilization of specific...... brain areas responsible for the emergence of the individual´s explicit and variable access to given segments of such broadcast. Rather than advocating one model over others, this chapter proposes to broaden the conceptualization of consciousness by letting it embrace both mechanisms. Within...... such extended framework, I propose conceptual and functional distinctions between consciousness (global broadcast of information), awareness (individual´s ability to access the content of such broadcast) and unconsciousness (focally isolated neural activations). My hypothesis is that a demarcation in terms...

  6. Does switching from oral extended-release methylphenidate to the methylphenidate transdermal system affect health-related quality-of-life and medication satisfaction for children with attention-deficit/hyperactivity disorder?

    Directory of Open Access Journals (Sweden)

    Landgraf Jeanne M

    2009-12-01

    Full Text Available Abstract Background To evaluate health-related quality of life (HRQL and medication satisfaction after switching from a stable dose of oral extended-release methylphenidate (ER-MPH to methylphenidate transdermal system (MTS via a dose-transition schedule in children with attention-deficit/hyperactivity disorder (ADHD. Methods In a 4-week, multisite, open-label study, 171 children (164 in the intent-to-treat [ITT] population aged 6-12 years diagnosed with ADHD abruptly switched from a stable dose of oral ER-MPH to MTS nominal dosages of 10, 15, 20, and 30 mg using a predefined dose-transition schedule. Subjects remained on the scheduled dose for the first week, after which the dose was then titrated to an optimal effect. The ADHD Impact Module-Children (AIM-C, a disease-specific validated HRQL survey instrument measuring child and family impact, was used to assess the impact of ADHD symptoms on the lives of children and their families at baseline and study endpoint. Satisfaction with MTS use was assessed via a Medication Satisfaction Survey (MSS at study endpoint. Both the AIM-C and MSS were completed by a caregiver (parent/legally authorized representative. Tolerability was monitored by spontaneous adverse event (AE reporting. Results AIM-C child and family HRQL mean scores were above the median possible score at baseline and were further improved at endpoint across all MTS doses. Similar improvements were noted for behavior, missed doses, worry, and economic impact AIM-C item scores. Overall, 93.8% of caregivers indicated a high level of satisfaction with their child's use of the study medication. The majority of treatment-emergent AEs (> 98% were mild to moderate in intensity, and the most commonly reported AEs included headache, decreased appetite, insomnia, and abdominal pain. Seven subjects discontinued the study due to intolerable AEs (n = 3 and application site reactions (n = 4. Conclusion This study demonstrates that MTS, when carefully

  7. The safety and effectiveness of open-label extended-release carbamazepine in the treatment of children and adolescents with bipolar I disorder suffering from a manic or mixed episode

    Directory of Open Access Journals (Sweden)

    Findling RL

    2014-08-01

    Full Text Available Robert L Findling,1,2 Lawrence D Ginsberg31Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, 2Kennedy Krieger Institute, Baltimore, MD, USA; 3Red Oak Psychiatry Associates, PA, Houston, TX, USAObjective: To assess the safety and effectiveness of open-label treatment with extended-release carbamazepine (ERC in pediatric subjects suffering from bipolar I disorder.Method: Medically healthy youths aged 10–17 years suffering from an acute manic or mixed episode were eligible. After screening for study eligibility, the youths began a 5-week titration period in which doses of ERC were adjusted in order to optimize benefit whilst minimizing adverse events, at doses between 200–1,200 mg/day. Thereafter, subjects could continue to receive treatment during a subsequent 21-week period. Safety measures included spontaneously reported adverse events (AEs and laboratory assessments. The primary efficacy measure was the Young Mania Rating Scale (YMRS.Results: A total of 60 children (ages 10–12 and 97 adolescents (ages 13–17, with an overall average age of 13.4 years (standard deviation [SD] 2.0 years received ERC. The mean duration of study participation was 109.6 days (SD 70.2 days, with 66 (42% completing the entire study. At end of study participation (end point, the most prevalent dose of ERC was 1,200 mg: 31.7% of children and 24.7% of adolescents reached the 1,200 mg dose. The YMRS decreased from a mean of 28.6 (SD 6.2 at baseline to a mean of 13.8 (SD 9.4 (P<0.0001 at end point. A total of 26 subjects discontinued study participation because of AEs, the most common of which were rash (n=6, white blood cell count decreased (n=5, nausea (n=3, and vomiting (n=3. No deaths were reported. The most commonly reported AEs were headache (n=41, somnolence (n=30, nausea (n=22, dizziness (n=21, and fatigue (n=19.Conclusions: Open-label administration of ERC might be a safe

  8. Effects of extended-release niacin on the postprandial metabolism of Lp(a) and ApoB-100-containing lipoproteins in statin-treated men with type 2 diabetes mellitus.

    Science.gov (United States)

    Ooi, Esther M; Watts, Gerald F; Chan, Dick C; Pang, Jing; Tenneti, Vijay S; Hamilton, Sandra J; McCormick, Sally P; Marcovina, Santica M; Barrett, P Hugh R

    2015-12-01

    The effects of extended-release niacin (ERN; 1-2 g/d) on the metabolism of lipoprotein(a) (Lp(a)) and apolipoprotein (apo) B-100-containing lipoproteins were investigated in 11 statin-treated white men with type 2 diabetes mellitus in a randomized, crossover trial of 12-weeks duration. The kinetics of Lp(a) and very low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) apoB-100 were determined following a standardized oral fat load (87% fat) using intravenous administration of D3-leucine, gas chromatography-mass spectrometry, and compartmental modeling. ERN significantly decreased fasting plasma total cholesterol, LDL cholesterol, and triglyceride concentrations. These effects were achieved without significant changes in body weight or insulin resistance. ERN significantly decreased plasma Lp(a) concentration (-26.5%) and the production rates of apo(a) (-41.5%) and Lp(a)-apoB-100 (-32.1%); the effect was greater in individuals with elevated Lp(a) concentration. ERN significantly decreased VLDL (-58.7%), intermediate-density lipoprotein (-33.6%), and LDL (-18.3%) apoB-100 concentrations and the corresponding production rates (VLDL, -49.8%; intermediate-density lipoprotein, -44.7%; LDL, -46.1%). The number of VLDL apoB-100 particles secreted increased in response to the oral fat load. Despite this, total VLDL apoB-100 production over the 10-hour postprandial period was significantly decreased with ERN (-21.9%). In statin-treated men with type 2 diabetes mellitus, ERN decreased plasma Lp(a) concentrations by decreasing the production of apo(a) and Lp(a)-apoB-100. ERN also decreased the concentrations of apoB-100-containing lipoproteins by decreasing VLDL production and the transport of these particles down the VLDL to LDL cascade. Our study provides further mechanistic insights into the lipid-regulating effects of ERN. © 2015 American Heart Association, Inc.

  9. Quality measure attainment with dapagliflozin plus metformin extended-release as initial combination therapy in patients with type 2 diabetes: a post hoc pooled analysis of two clinical studies

    Directory of Open Access Journals (Sweden)

    Bell KF

    2016-10-01

    Full Text Available Kelly F Bell, Arie Katz, John J Sheehan AstraZeneca, Wilmington, DE, USA Background: The use of quality measures attempts to improve safety and health outcomes and to reduce costs. In two Phase III trials in treatment-naive patients with type 2 diabetes, dapagliflozin 5 or 10 mg/d as initial combination therapy with metformin extended-release (XR significantly reduced glycated hemoglobin (A1C from baseline to 24 weeks and allowed higher proportions of patients to achieve A1C <7% vs dapagliflozin or metformin monotherapy. Objective: A pooled analysis of data from these two studies assessed the effect of dapagliflozin 5 or 10 mg/d plus metformin XR (combination therapy compared with placebo plus metformin XR (metformin monotherapy on diabetes quality measures. Quality measures include laboratory measures of A1C and low-density lipoprotein cholesterol (LDL-C as well as vital status measures of blood pressure (BP and body mass index (BMI. The proportion of patients achieving A1C, BP, and LDL-C individual and composite measures was assessed, as was the proportion with baseline BMI ≥25 kg/m2 who lost ≥4.5 kg. Subgroup analyses by baseline BMI were also performed. Results: A total of 194 and 211 patients were treated with dapagliflozin 5- or 10-mg/d combination therapy, respectively, and 409 with metformin monotherapy. Significantly higher proportions of patients achieved A1C ≤6.5%, <7%, or <8% with combination therapy vs metformin monotherapy (P<0.02. Significantly higher proportions of patients achieved BP <140/90 mmHg (P<0.02 for each dapagliflozin dose and BP <130/80 mmHg (P<0.02 with dapagliflozin 5 mg/d only with combination therapy vs metformin monotherapy. Similar proportions (29%–33% of patients had LDL-C <100 mg/dL across treatment groups. A higher proportion of patients with baseline BMI ≥25 kg/m2 lost ≥4.5 kg with combination therapy. Combination therapy had a more robust effect on patients with higher baseline BMI. Conclusion

  10. Extended-release niacin therapy and risk of ischemic stroke in patients with cardiovascular disease: the Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcome (AIM-HIGH) trial.

    Science.gov (United States)

    Teo, Koon K; Goldstein, Larry B; Chaitman, Bernard R; Grant, Shannon; Weintraub, William S; Anderson, David C; Sila, Cathy A; Cruz-Flores, Salvador; Padley, Robert J; Kostuk, William J; Boden, William E

    2013-10-01

    In Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial, addition of extended-release niacin (ERN) to simvastatin in participants with established cardiovascular disease, low high-density lipoprotein cholesterol, and high triglycerides had no incremental benefit, despite increases in high-density lipoprotein cholesterol. Preliminary analysis based on incomplete end point adjudication suggested increased ischemic stroke risk among participants randomized to ERN. This final analysis was conducted after complete AIM-HIGH event ascertainment to further explore potential relationship between niacin therapy and ischemic stroke risk. There was no group difference in trial primary composite end point at a mean 36-month follow-up among 3414 patients (85% men; mean age, 64±9 years) randomized to simvastatin plus ERN (1500-2000 mg/d) versus simvastatin plus matching placebo. In the intention-to-treat analysis, there were 50 fatal or nonfatal ischemic strokes: 18 (1.06%) in placebo arm versus 32 (1.86%) in ERN arm (hazard ratio [HR], 1.78 [95% confidence interval {CI}, 1.00-3.17; P=0.050). Multivariate analysis showed independent associations between ischemic stroke risk and >65 years of age (HR, 3.58; 95% CI, 1.82-7.05; P=0.0002), history of stroke/transient ischemic attack/carotid disease (HR, 2.18; 95% CI, 1.23-3.88; P=0.0079), elevated baseline Lp(a) (HR, 2.80; 95% CI, 1.25-6.27 comparing the middle with the lowest tertile; HR, 2.31; 95% CI, 1.002-5.30 comparing the highest with the lowest tertile; overall P=0.042) but a nonsignificant association with ERN (HR, 1.74; 95% CI, 0.97-3.11; P=0.063). Although there were numerically more ischemic strokes with addition of ERN to simvastatin that reached nominal significance, the number was small, and multivariable analysis accounting for known risk factors did not support a significant association between niacin and ischemic stroke risk. http

  11. Extended Chameleons

    CERN Document Server

    Brax, Philippe

    2015-01-01

    We extend the chameleon models by considering Scalar-Fluid theories where the coupling between matter and the scalar field can be represented by a quadratic effective potential with density-dependent minimum and mass. In this context, we study the effects of the scalar field on Solar System tests of gravity and show that models passing these stringent constraints can still induce large modifications of Newton's law on galactic scales. On these scales we analyse models which could lead to a percent deviation of Newton's law outside the virial radius. We then model the dark matter halo as a Navarro-Frenk-White profile and explicitly find that the fifth force can give large contributions around the galactic core in a particular model where the scalar field mass is constant and the minimum of its potential varies linearly with the matter density. At cosmological distances, we find that this model does not alter the growth of large scale structures and therefore would be best tested on galactic scales, where inter...

  12. Behavioural and pharmacological effects of fluvoxamine on decision-making in food patches and the inter-temporal choices of domestic chicks.

    Science.gov (United States)

    Matsunami, Shohei; Ogura, Yukiko; Amita, Hidetoshi; Izumi, Takeshi; Yoshioka, Mitsuhiro; Matsushima, Toshiya

    2012-08-01

    Behavioural effects of fluvoxamine (FLV, selective serotonin reuptake inhibitor) were examined in 1-2 week old domestic chicks. Chicks were tested in an I-shaped maze equipped with a feeder (ON feeder) that served 1 or 2 grains of millet at gradually increasing intervals, so that a depleting food patch was mimicked. By leaving the feeder, the food delivery program was reset, and chicks gained food at short intervals only after a travel to a dummy feeder (OFF feeder) placed on the opposite side of the maze. Chicks quickly learned to actively shuttle between the ON and the OFF feeders. FLV (intra-peritoneal injection, 20 mg/kg BW) acutely caused chicks to stay longer at the gradually depleting ON feeder. Inter-temporal choices were also tested, whereby two coloured beads were simultaneously presented, each associated with a small/short-delay reward or a large/long-delay alternative. FLV suppressed the choice of the short-delay option. It is suggested that an enhanced level of serotonin (5-HT) makes chicks more tolerant of the delayed food item in both behavioural paradigms. Furthermore, the decision to leave a depleting patch cannot be equated to choosing the long-delay option of the choice paradigm. Furthermore, FLV suppressed work efforts (velocity and running distance) in uncued shuttle and number of distress calls. In vivo microdialysis experiments revealed that FLV enhanced the extracellular concentration of 5-HT as well as dopamine (DA) locally in the medial striatum/nucleus accumbens. Underlying neuromodulatory mechanisms of behavioural control are examined in relation to locomotion, behavioural tolerance and interval timing.

  13. Evaluation of Patient Migration Patterns and Related Health Care Costs Within a National Medicare Advantage Prescription Drug Plan After Implementation of an Oxycodone HCl Extended-Release Access Restriction.

    Science.gov (United States)

    Chen, Chi-Chang; De, Ajita P; Sweet, Brian; Wade, Rolin L

    2017-08-01

    Health plans use formulary restrictions (e.g., prior authorization, step therapy, tier change, nonformulary status) in an effort to control cost and promote quality, safety, and appropriate prescription utilization. Some Medicare payers perceive that the inclusion of certain agents, such as branded oxycodone HCl extended-release tablets (OERs), on their formularies is associated with attracting high-cost members to the plan. To evaluate disenrollment rates, patient migration, and subsequent health care costs among OER users who disenrolled from a national Medicare Advantage Prescription Drug plan (study-MAPD) in the plan year following OER nonformulary restriction. A retrospective, longitudinal cohort study using IMS pharmacy and medical claims data between July 1, 2011, and December 31, 2014, was conducted. In the study-MAPD, adults aged ≥ 18 years who were chronic OER users with ≥ 2 OER claims 6 months before the nonformulary restriction date on January 1, 2013 (index date) and with continuous activity in pharmacy and medical claims for 6 months pre- and post-index were included in the study. Comparison years of 2012 and 2014 prerestriction/postrestriction were selected. All groups were followed for 6 months postindex. Year-to-year disenrollment rates of OER patients and the overall plan, as well as patient characteristics and costs of those who disenrolled from and those who remained with the plan, were measured. Costs were compared using a difference-in-differences approach. This study identified 2,935 eligible OER users from the study-MAPD population after imposing nonformulary restrictions on OERs on January 1, 2013. Mean age was 62.1 years, and 59.8% were female. The mean Charlson Comorbidity Index score was 1.83 for those 1,001 patients with medical claims data. For comparison years 2012 (prerestriction) and 2014 (postrestriction), 2,248 and 2,222 OER patients were identified, respectively. Patient characteristics were similar across patient cohorts in

  14. The efficacy of gabapentin extended-release tablets for the treatment of postherpetic neuralgia: a meta analysis%加巴喷丁缓释片治疗带状疱疹后神经痛效果的Meta分析

    Institute of Scientific and Technical Information of China (English)

    朱琳; 蒋宗滨

    2012-01-01

    目的 系统评价加巴喷丁缓释片单次服用和分次服用治疗带状疱疹后神经痛( postherpetic neuralgia,PHN)的临床效果.方法 电子检索Cochran图书馆临床对照试验资料库、PubMed、EMbase、中国生物医学数据库、维普、知网及万方数据库,收集比较加巴喷丁缓释片单次服用和分次服用治疗PHN的随机对照试验(RCT).采用RevMan 5.0软件对数据进行Meta分析.结果有2篇RCT论文符合标准纳入分析,共379例患者.Meta分析结果显示:(1)加巴喷丁缓释片单次服和分次服相比治疗PHN的有效性差异无统计学意义;(2)加巴喷丁缓释片单次服和分次服相比治疗PHN的不良反应的发生率差异无统计学意义.结论 加巴喷丁缓释片单次和分次服用治疗PHN的效果和不良反应相同.%Objective To systemically review the clinical efficacy of gabapentin extended-release (gabapentin ER) tablets taken once-daily or in split-dose for the treatment of postherpetic neuralgia(PHN). Methods The randomized controlled trials(RCTs) of gabapentin ER tablets taken once-daily or in split-dose for the treatment of PHN were retrieved from Cochran Central Register of Controlled Trials, PubMed, Embase, China biomedical database (CBM) , VfP Chinese technology periodical database(PSTP) , Tsinghua tongfang database(CNKI) and WanFang database(Chianlnfo). Meta-analysis was performed using Revman 5. 0 software. Results Two RCTs met all the criteria and were enrolled in this review, including 379 patients. The results of mcta-analysis indicated that the effectiveness of gabapentin ER administered once-daily or in split-dose for treatment of PHN was not significantly different, and the incidence of adverse effects of gabapentin ER taken once-daily or in split-dose for treatment of PHN was not significantly different. Conclusion Gabapentin ER administered once-daily or in split-dose has the same effectiveness and adverse effects for the treatment of postherpetic

  15. Pharmacokinetics of venlafaxine extended release 75  mg and desvenlafaxine 50  mg in healthy CYP2D6 extensive and poor metabolizers: a randomized, open-label, two-period, parallel-group, crossover study.

    Science.gov (United States)

    Nichols, Alice I; Focht, Kristen; Jiang, Qin; Preskorn, Sheldon H; Kane, Cecelia P

    2011-01-01

    Genetically driven variations in the level of cytochrome P450 (CYP) 2D6 metabolic activity have been shown to significantly affect the pharmacokinetic behaviour of medications that are substrates of this enzyme. To evaluate the impact of CYP2D6 extensive metabolizer (EM) and poor metabolizer (PM) phenotypes on the pharmacokinetics of single doses of venlafaxine extended release (ER) and desvenlafaxine (administered as desvenlafaxine succinate). This study used a randomized, open-label, two-period, parallel-group, crossover design. The enrolled healthy subjects participated in the study for approximately 8 weeks, which included ≤ 6 weeks of screening procedures and two separate 1-week partial inpatient confinement periods (separated by a 4-day washout period), during which venlafaxine ER or desvenlafaxine was administered and blood samples were collected. Subjects were admitted to partial inpatient confinement in a laboratory setting for the two separate study periods where each study drug was individually administered. Blood samples for pharmacokinetic analyses were collected during the 120 hours following administration of each study drug. Plasma concentrations of the study drugs were measured by a third-party analyst using liquid chromatography-tandem mass spectrometry. Healthy subjects were recruited through newspaper advertisements and genotyped to determine their CYP2D6 metabolic phenotype (i.e. EM or PM) using internally developed and commercially available assays. Subjects were reimbursed for their participation in this study. Single, sequentially administered oral doses of the dual-acting, serotonin and norepinephrine reuptake inhibiting antidepressants venlafaxine ER (75  mg) and desvenlafaxine (50  mg) were administered. The main outcome measures were differences in the geometric means for area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) and peak plasma concentration (C(max)) between EMs and PMs. Comparisons were

  16. 氟伏沙明治疗强迫症的疗效和对生活质量的影响%Effect of fluvoxamine in treatment of obsessive-compulsive disorder and the effect on quality of life

    Institute of Scientific and Technical Information of China (English)

    王东明; 孙平; 段妮

    2016-01-01

    目的:观察氟伏沙明治疗强迫症的疗效和对患者生活质量的影响。方法将60例强迫症患者随机分为2组各30例。分别应用氟伏沙明和氯丙咪嗪治疗,应用 Y-BOCS 量表和 GQOLI-74量表进行评估,比较2组疗效和患者生活质量的变化以及不良反应。结果治疗前2组患者 Y-BOCS 评分比较差异无统计学意义(P ﹥0.05)。治疗第1周末至第12周末,2组 Y-BOCS 评分均低于治疗前,差异均有统计学意义(P ﹤0.05或 P ﹤0.01)。治疗后组间比较差异无统计学意义(P ﹥0.05)。治疗12周末,2组患者躯体功能、心理功能、社会功能评分均高于治疗前,差异均有统计学意义(P ﹤0.01)。在治疗12周末,氟伏沙明组患者的躯体功能和社会功能评分均明显高于氯丙咪嗪组,差异均有统计学意义(P ﹤0.01)。氟伏沙明组不良反应较氯丙咪嗪组少且轻。结论氟伏沙明治疗强迫症安全有效,同时较好地改善患者的生活质量,值得临床推广。%Objective To observe the effect of fluvoxamine in treatment of obsessive-compulsive disorder and the effect on quality of life. Methods 60 patients with obsessive-compulsive disorder were randomly divided into two groups with 30 cases each. These two groups were treated by fluvoxamine and clomipramine respectively. The efficacy and quality of life were measured with Yale-Brown Obsessive Compulsive Scale(Y-BOCS)and general quality of life inventory-74(GQOLI-74) before and during the 12 weeks treatment. Results There were no difference between the two groups in scores of Y-BOCS be-fore treatment(P ﹥ 0. 05). At the end of 1st to 12th week of the treatment,score of the Y-BOCS all reduced gradually in two groups(P ﹤ 0. 05 or P ﹤ 0. 01),but over the same period there was no significant difference between the two groups. At the end 12th week,two groups both have significant improve in physical function,psychological function

  17. Clinical Observation on Fluvoxamine and Aripiprazole as Adjunctive Therapy in the Treatment of Obsessive-compulsive Disorders%阿立哌唑辅助氟伏沙明治疗强迫障碍的临床观察

    Institute of Scientific and Technical Information of China (English)

    魏宏强; 康瑞; 李爱玲; 赵秀娟

    2013-01-01

    Objective:To explore the efficacy and safety of fluvoxamine and aripiprazole as adjunctive therapy in the treatment of obsessive-compulsive disorders patients.Method:Total 54 obsessive-compulsive disorders patients were randomly divided into two groups:Fluvoxamine(250-300 mg/d)auxiliaried by aripiprazole(2.5-10 mg/d)group(study group)and fluvoxamine(250-300 mg/d)group(contral group),27 for each. Each group had a 8-week treatment.The efficacy were assessed and analyzed by Yale-Brown Obsessive Compulsive Scale(Y-BOCS) at baseline and at week 2,4,6 and 8. The side effects were assessed by Treatment Emergent Syptom Scale(TESS)during the treatment. Result:Study group and contral group had 1,2 case being off respectively. The obsession and compulsion scores of study group had all statistical difference at baseline and week 2,4 ,6,8 each other(P0.05). At week 4,in both groups,the compulsion scores had statistical difference(P0.05). Conclusion:Fluvoxamine and aripiprazole as adjunctive therapy can effectively continue to improve the compulsive symptoms in the treatment of obsessive-compulsive disorders patients,the rate of side effects is similar to that of simple fluvoxamine therapy.%  目的:探讨阿立哌唑辅助氟伏沙明治疗强迫障碍的临床疗效及安全性.方法:将54例强迫障碍患者随机分为两组(各27例):阿立哌唑(2.5~10 mg/d)辅助氟伏沙明(250~300 mg/d)组(研究组)、氟伏沙明(250~300 mg/d)组(对照组),治疗观察期均为8周.两组患者于基线及治疗2、4、6、8周末分别评定Yale-Brown强迫量表(Y-BOCS),并采用副反应量表(TESS)评定治疗期间的不良反应.结果:研究组、对照组分别脱落1例、2例.研究组的强迫思维和强迫行为评分在基线及2、4、6、8周末时点间比较差异均有统计学意义(P0.05);4周末时,两组间的强迫行为评分比较差异有统计学意义(P0.05).结论:阿立哌唑辅助氟伏沙明可有效、持续地改善强迫障

  18. Neuroleptic malignant syndrome due to concomitant use of olanzapine and fluvoxamine%奥氮平联用氟伏沙明致恶性综合征

    Institute of Scientific and Technical Information of China (English)

    孙振晓; 李景君

    2016-01-01

    1例72岁男性抑郁症患者应用奥氮平(7.5 mg/ d)合并氟伏沙明(125 mg/ d)口服治疗2个月后出现发热、意识障碍、肌强直、多汗、心动过速,WBC 12.3×109/ L,血清 CK 737 U/ L。停用所有口服药物,给予持续吸氧、心电监护、保持呼吸道通畅、物理降温、维持水电解质及酸碱平衡、控制感染等处置,并静脉滴注氯硝西泮1 mg/ d,口服多巴胺受体激动剂吡贝地尔100 mg/ d。3 d 后患者体温恢复正常,意识转清,5 d 后肌张力及血常规各项指标和血清 CK 恢复正常。%A 72-year-old man with depression received oral olanzapine 7. 5 mg/ d and fluvoxamine 125 mg/ d. Two months after the drug administration,the patient developed fever,consciousness,rigidity, sweating,and tachycardia. Blood tests showed that the white blood cell count was 12. 3 × 109 / L and creatine kinase( CK ) level was 737 U/ L. All drugs were stopped and continuous oxygen inhalation, electrocardiographic monitoring and measures for keeping the respiratory tract unobstructed were given. Ice pillows and ice packs were used to lower his temperature. Treatments such as fluid infusion,correction of water-electrolyte balance,infection prevention,intravenous infusion of clonazepam 1 mg once daily,and oral dopamine receptor agonist piribedil 100 mg once daily were also given. Three days later,his temperature returned to normal and his consciousness turned clear. Five days later,his muscle tension,routine blood test,and CK level returned to normal.

  19. AnalysisoftheClinicalEffectofControlled-releaseTabletsintheTreatmentofDiabetesMellituswithGlipizideExtended%应用格列吡嗪控释片治疗糖尿病的临床效果分析

    Institute of Scientific and Technical Information of China (English)

    胡少辉

    2013-01-01

    Objective To observe the clinical effect of controlled-release glipizide in treating type 2 diabetes mellitus. Methods The diabetic patients in our hospital from 120 cases, were randomly divided into observation group and control group, patients in the observation group use controlled-release Glipizide treatment, the patients in control group were treated with metformin. Results The patients in the two groups after treatment , FBG , F2BG , TC , TG , LDL , decreased significantly, and the patients in the observation group decreased significantly than the control group, the difference was statistically significant (P<0.05 ). Conclusion The use of glipizide controlled-release tablets in the treatment of diabetes, can effectively reduce the blood glucose and lipid levels in patients with metformin, compared with more good clinical effect.%  目的观察分析使用格列吡嗪控释片治疗2型糖尿病的临床疗效。方法从我院收治的糖尿病患者中抽取120例,随机分为观察组与对照组,观察组患者使用格列吡嗪控释片进行治疗,对照组患者使用二甲双胍进行治疗,对比观察两组患者的临床效果。结果治疗后两组患者的空腹血糖(FBG)、餐后2h血糖(F2BG)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL)等出现明显下降,且观察组患者下降程度明显多于对照组,差异有统计学意义(P<0.05)。结论使用格列吡嗪控释片治疗糖尿病,能够有效降低患者血糖及血脂水平,相比二甲双胍具有更为理想的临床疗效。

  20. Controlled-release microchips.

    Science.gov (United States)

    Sharma, Sadhana; Nijdam, A Jasper; Sinha, Piyush M; Walczak, Robbie J; Liu, Xuewu; Cheng, Mark M-C; Ferrari, Mauro

    2006-05-01

    Efficient drug delivery remains an important challenge in medicine: continuous release of therapeutic agents over extended time periods in accordance with a predetermined temporal profile; local delivery at a constant rate to the tumour microenvironment to overcome much of the systemic toxicity and to improve antitumour efficacy; improved ease of administration, and increasing patient compliance required are some of the unmet needs of the present drug delivery technology. Microfabrication technology has enabled the development of novel controlled-release microchips with capabilities not present in the current treatment modalities. In this review, the current status and future prospects of different types of controlled-release microchips are summarised and analysed with reference to microneedle-based microchips, as well as providing an in-depth focus on microreservoir-based and nanoporous microchips.

  1. On generalized extending modules

    Institute of Scientific and Technical Information of China (English)

    ZENG Qing-yi

    2007-01-01

    A module M is called generalized extending if for any submodule N of M, there is a direct summand K of M such that N≤K and K/N is singular. Any extending module and any singular module are generalized extending. Any homomorphic image of a generalized extending module is generalized extending. Any direct sum of a singular (uniform) module and a semi-simple module is generalized extending. A ring R is a right Co-H-ring ifand only ifall right R modules are generalized extending modules.

  2. Relationship between the dopamine D2 receptor gene polymorphism and efficacy of paliperidone extended release tablets%多巴胺D2受体基因多态性与帕利哌酮缓释片疗效的相关性

    Institute of Scientific and Technical Information of China (English)

    刘向来; 黄胜; 林展; 郑在激; 陈雄

    2014-01-01

    Objective To investigate the relationship between the dopa-mine D2 receptor ( DRD2 ) gene polymorphism and efficacy of paliperi-done extended release tablets.Methods Eighty schizophrenia patients ( the Han nationality ) were included in the study.They were administra-ted with pailperidone extended -release tablets(6-12 mg· d-1 ) for six weeks and assessed with positive and negative symptoms scale ( PANSS) and the other four kinds of scores before and after treatment.They were divided into responsive group ( the reduction rate ≥50%) and unrespon-sive group ( the reduction rate 0.05).Conclusion DRD2 gene polymorphism and the efficacy of paliperidone extended -release tablets in Han nationality patients with schizophrenia may be not related .%目的:观察多巴胺D2受体( DRD2)基因多态性与帕利哌酮缓释片疗效之间的关系。方法随机抽取80例汉族精神分裂症患者,给予帕利哌酮缓释片6~12 mg· d-1治疗6周。治疗前后,用阳性和阴性症状量表( PANSS)及各分量表评定帕利哌酮缓释片疗效;按PANSS减分率≥50%和<50%,分为有效组和无效组,用基因扩增的限制性片段长度多态技术对2组的精神分裂症患者与DRD2基因进行遗传关联分析。结果治疗前后,PANSS总分及各分量表评分比较差异有统计学意义( P<0.01);2组在等位基因频率及基因型频率的差异无统计学意义( P>0.05)。结论在汉族精神分裂症患者中DRD2基因(-141 C Ins/Del)多态性与帕利哌酮缓释片疗效之间可能不存在相关性。

  3. 帕利哌酮缓释片和奥氮平治疗首发精神分裂症的对照研究%A control study of paliperidone extended - release tablets and olanzapine in the treatment of first - episode schizophrenia

    Institute of Scientific and Technical Information of China (English)

    毛智群; 李达; 查智群; 顾曙光; 季萍

    2011-01-01

    Objective To compare efficacy and safety of paliperidone extended -release tablets and olanzapine in the treatment of first - episode schizophrenia. Methods 90 adult patients with first - episode schizophrenia in accordance with CCMD - HI were randomized into study group treated with paliperidone extended - release tablets and control group treated with olanzapine for 8 weeks. The Positive and Nenative Syndrome Scale ( PANSS) and Treatment Emergent Side effect Scale ( TESS) were used to evaluate efficacy and side effects respectively at the baseline and at the ends of the 2nd, 4th and 8th weekends of the treatment. Results There was no significant difference in effective rate between study group and control group (91. 2% vs. 96. 5% , P >0. 05). Total score and factor scores of PANSS at each interview - point showed no significant differences between the two groups ( P > 0.05 ). The incidence rate of side effects in both groups was low and the severity was mild. Conclusion Paliperidone extended - release tablets have equivalent efficacy and safety in the treatment of first - episode schizophrenia.%目的 评价帕利哌酮缓释片和奥氮平治疗首发精神分裂症的疗效和安全性.方法 对符合CCMD -3中首发精神分裂症诊断标准的90例患者,随机分为帕利哌酮缓释片组和奥氮平组,分别治疗8周.采用阳性和阴性症状量表( PANSS)和副反应量表(TESS)评定疗效及副反应.结果 帕利哌酮缓释片组有效率为91.2%,奥氮平组有效率为96.5%,差异无统计学意义(P>0.05);两组治疗前后各时点PANSS总分及各因子分比较差异均无统计学意义(P>0.05).两组治疗中的不良反应发生率低、程度轻.结论 帕利哌酮缓释片与奥氮平治疗首发精神分裂症疗效相当,不良反应轻.两种药物均为疗效好、安全性高的抗精神病药.

  4. Extended Dislocations in Plastically Deformed Metallic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Bin Zheng

    2016-05-01

    Full Text Available In the present study, the sawtooth nature of compressive loading of metallic nanoparticles is observed using a molecular dynamics simulation. The atomic structure evolution confirmed that extended dislocations are the main defects split into two asynchronous partial disloca‐ tions, along with stored and released fault energy. This is considered the essence of sawtooth loading. The size of the nanoparticles relative to the equilibrium width of the extended dislocation is discussed to explain the simulation results.

  5. 氟伏沙明联合认知行为疗法在强迫症治疗中的应用价值%Use of Fluvoxamine and cognitive behavioral therapy in treatment of obsessive-compulsive disorder

    Institute of Scientific and Technical Information of China (English)

    王春江; 黄鹏; 林伟成

    2016-01-01

    目的:探讨氟伏沙明联合认知行为疗法在强迫症治疗中的应用价值。方法:将2014年3月至2015年2月广州市惠爱医院收治的120例强迫症患者随机分为观察组(氟伏沙明联合认知行为疗法)和对照组(单用氟伏沙明),每组各60例,疗程共12个月。随访6、12个月,采用Y-BOCS减分率评定标准和自我和谐量表进行评估,对比两组临床疗效、依从性及复发率等指标差异。结果:治疗后6、12个月,观察组痊愈率、有效率均显著优于对照组(P<0.01);两组Y-BOCS评分、自我和谐量表评分均优于治疗前(P<0.05),其中观察组优于对照组(P<0.01);观察组治疗依从性均好于对照组。治疗后12个月,对照组和观察组中出现过复发或恶化者分别为22例(36.7%)和9例(15.0%),两组比较,差异有统计学意义(P<0.01)。结论:氟伏沙明联合认知行为疗法治疗强迫症远期疗效显著,依从性好,复发率低,优于单用氟伏沙明治疗。%Objective:To investigate the use of Fluvoxamine and cognitive behavioral therapy in the treatment of obsessive-compulsive disorder. Methods:A total of 120 patients with obsessive-compulsive disorder, who were hospitalized in Guangzhou Huiai Hospital between March 2014 and February 2015,were randomly divided into the study group (Fluvoxamine and cognitive behavioral therapy)and the control group (monotherapy with Fluvoxamine),with 60 cases in each group,and a course of treatment for 12 months. All patients were followed up for 6 and 12 months. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)reduction rate and Self Consistency and Congruence Scale (SCCS ) were used for evaluation. The clinical effect,compliance and recurrence rate in the two groups were compared. Results:At 6 and 12 months after the treatment,the cure rate and effective rate in the study group were significantly better than those in the

  6. Locomotor therapy with extended-release crystalline glucocorticoids

    Directory of Open Access Journals (Sweden)

    Vladimir Vasilyevich Badokin

    2013-01-01

    Full Text Available Topical glucocorticoid (GC therapy for locomotor diseases is an extremely important component of a comprehensive program to treat inflammatory and, to a lesser extent, degenerative diseases. It reduces the time of hospitalization by 5—10 days in this category of patients, has a prompt and potent anti-inflammatory effect, and shows predictable efficiency. This therapy shows good tolerability and high safety and prevents serious adverse reactions to GC treatment.

  7. Extended-release hydrocodone – gift or curse?

    Directory of Open Access Journals (Sweden)

    Krashin D

    2013-01-01

    Full Text Available Daniel Krashin,1 Natalia Murinova,2 Andrea M Trescot31Department of Anesthesiology and Pain Medicine, 2Department of Neurology University of Washington, Seattle, WA, USA 3Algone Pain Center, Wasilla, AK, USAAbstract: Hydrocodone is a semisynthetic opioid, which has been used for decades as a short-acting analgesic combined with acetaminophen (or less commonly ibuprofen. Several long-acting, non-acetaminophen-containing hydrocodone formulations are undergoing trials in the US under the auspices of the US Food and Drug Administration, and may be available shortly. This article reviews some of the advantages (including drug familiarity and lack of acetaminophen toxicity and potential disadvantages (including altered use patterns and high morphine equivalent dosing of such a medication formulation. We also discuss the abuse potential of long-acting versus short-acting opioids in general and hydrocodone specifically, as well as the metabolism of hydrocodone.Keywords: hydrocodone, long-acting opioids, opioid abuse, acetaminophen toxicity, tamper-resistant opioids

  8. Extended Life Coolant Testing

    Science.gov (United States)

    2016-06-06

    ELC – Extended Life Coolant SCA – Supplemental Coolant Additive SOW – Scope of Work SwRI – Southwest Research Institute TARDEC – Tank Automotive...ethylene or propylene glycol and 35% extended life coolant #1 (ELC1) with a balance of water. At a higher ELC1 content of 45% or 50%, the mass loss...UNCLASSIFIED TABLE OF CONTENTS EXTENDED LIFE COOLANT TESTING INTERIM REPORT TFLRF No. 478 by Gregory A. T. Hansen Edwin A

  9. Extended icosahedral structures

    CERN Document Server

    Jaric, Marko V

    1989-01-01

    Extended Icosahedral Structures discusses the concepts about crystal structures with extended icosahedral symmetry. This book is organized into six chapters that focus on actual modeling of extended icosahedral crystal structures. This text first presents a tiling approach to the modeling of icosahedral quasiperiodic crystals. It then describes the models for icosahedral alloys based on random connections between icosahedral units, with particular emphasis on diffraction properties. Other chapters examine the glassy structures with only icosahedral orientational order and the extent of tra

  10. A Case of Treatment Resistant Depression and Alcohol Abuse in a Person with Mental Retardation: Response to Aripiprazole and Fluvoxamine Therapy upon Consideration of a Bipolar Diathesis after Repetitive Failure to Respond to Multiple Antidepressant Trials.

    Science.gov (United States)

    Fornaro, Michele; Ciampa, Giovanni; Mosti, Nicola; Del Carlo, Alessandra; Ceraudo, Giuseppe; Colicchio, Salvatore

    2010-01-01

    Mental Retardation (MR) is a developmental disability characterized by impairments in adaptive daily life skills and difficulties in social and interpersonal functioning. Since multiple causes may contribute to MR, associated clinical pictures may vary accordingly. Nevertheless, when psychiatric disorders as Treatment Resistant Depression (TRD) and/or alcohol abuse co-exist, their proper detection and management is often troublesome, essentially due to a limited vocabulary MR people could use to describe their symptoms, feelings and concerns, and the lack of reliable screening tools. Furthermore, MR people are among the most medicated subjects, with (over) prescription of antidepressants and/or typical antipsychotics being the rule rather than exception. Thus, treatment resistance or even worsening of depression, constitute frequent occurrences. This report describes the case of a person with MR who failed to respond to repetitive trials of antidepressant monotherapies, finally recovering using aripiprazole to fluvoxamine augmentation upon consideration of a putative bipolar diathesis for "agitated" TRD. Although further controlled investigations are needed to assess a putative bipolar diathesis in some cases of MR associated to TRD, prudence is advised in the long-term prescription of antidepressant monotherapies in such conditions.

  11. 帕利呱酮缓释片对精神分裂症患者急性期的个人和社会功能影响%Effects of paliperidone extended-release tablets on the personal and social functions in acute patients with schizophrenia

    Institute of Scientific and Technical Information of China (English)

    衷天懿; 秦玲; 姚明荣; 唐建良; 岳伟清

    2011-01-01

    Objective To explore the effects of paliperidone extended -release tablets ( paliperidone ER) on the personal and social functions in acute patients with schizophrenia. Methods Total 85 cases of patients with schizophrenia were randomly divided into paliperidone ER group (43 cases) and risperidone group (42 cases) , the treatment course is 6 weeks. Indicators include the effect of positive and negative symptom scale ( PANSS) and clinical global impression ( CGI) , personal and social function for the Chinese version of personal and social performance scale (PSP - CHN). Results After 6 weeks of treatment, early effective in paliperidone ER group more than in risperidone group, but the overall effect of the two groups are equivalent. The PSP score, useful activities in society, personal and social relations, self - care improvement in three dimensions in the paliperidone ER group better than the risperidone group. Conclusion Paliperidone ER extended - release tablets inacute patients with schizophrenia are significantly effects, and paliperidone ER are comprehensively improve personal and social functions of patients with schizophrenia.%目的 观察帕利呢酮缓释片对精神分裂症急性期患者个人和社会功能的影响.方法 将85例精神分裂症患者随机分为帕利呱酮组(43例)与利培酮组(42例),疗程6周.并采用阳性与阴性症状量表(PANSS)、临床总体印象量表(CGI)、个人和社会功能量表(PSP)中文版(PSP-CHN)评定.结果 治疗6周后,帕利呢酮组的早期疗效优于利培酮组,但2组总体疗效相当;而帕利呢酮组PSP评分以及对社会中有用的活动、个人和社会关系、自我照料三项维度的改善优于利培酮组.结论 帕利呢酮缓释片对治疗精神分裂症急性期患者的疗效显著,并能全面改善患者的个人和社会功能.

  12. Renin release

    DEFF Research Database (Denmark)

    Schweda, Frank; Friis, Ulla; Wagner, Charlotte;

    2007-01-01

    The aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in salt, volume, and blood pressure homeostasis of the body. Renin is mainly produced and released into circulation by the so-called juxtaglomerular epithelioid cells, located......, salt, and volume overload. In contrast, the events controlling the function of renin-secreting cells at the organ and cellular level are markedly less clear and remain mysterious in certain aspects. The unravelling of these mysteries has led to new and interesting insights into the process of renin...

  13. Quantum Extended Supersymmetries

    CERN Document Server

    Grigore, D R; Grigore, Dan Radu; Scharf, Gunter

    2003-01-01

    We analyse some quantum multiplets associated with extended supersymmetries. We study in detail the general form of the causal (anti)commutation relations. The condition of positivity of the scalar product imposes severe restrictions on the (quantum) model. It is problematic if one can find out quantum extensions of the standard model with extended supersymmetries.

  14. Extended Theories of Gravitation

    Directory of Open Access Journals (Sweden)

    Fatibene Lorenzo

    2013-09-01

    Full Text Available Extended theories of gravitation are naturally singled out by an analysis inspired by the Ehelers-Pirani-Schild framework. In this framework the structure of spacetime is described by a Weyl geometry which is enforced by dynamics. Standard General Relativity is just one possible theory within the class of extended theories of gravitation. Also all Palatini f(R theories are shown to be extended theories of gravitation. This more general setting allows a more general interpretation scheme and more general possible couplings between gravity and matter. The definitions and constructions of extended theories will be reviewed. A general interpretation scheme will be considered for extended theories and some examples will be considered.

  15. Evaluation of new polysaccharides networks for extended-release purposes: mesquite seed gum (MSG, xanthan gum and chitosan Estudo da utilização de polissacarídeos no desenvolvimento de formulações de liberação prolongada: goma de semente de algaroba, goma xantana e quitosano

    Directory of Open Access Journals (Sweden)

    Carlos César dos Santos Nogueira

    2003-09-01

    Full Text Available The aim of this work was to design new hydrophilic matrix (HM systems by cross-linking Mesquite Seed Gum (MSG, a galactomannan that occurs in the endosperm layer of the seeds of a Brazilian tree,Prosopis juliflora DC, with two well-known polysaccharides with the ability of retarding drug release, chitosan and xanthan gum. This had in mind the idea of using these new compounds in the preparation of extended-release dosage oral forms. The first part of this study was dedicated to the evaluation of MSG in terms of its functionality as a hydrophilic matrix (HM system for extended-release purposes. Next, we started the study of water uptake profile of all polymers of interest (MSG, Xanthan Gum and Chitosan, in the following media: water, SGF and SIF. Following, we searched for the best cross-linking agent between Glutharaldehyde (GA and Hexamethylenediisocyanate (HMDI, which turned out to be the GA. Next step we begun to prepare new hydrophilic matrices of MSG_Chitosan and MSG_Xanthan Gum, with different ratios, 1:1, 1:2 and 2:1. Finally, after deciding which new HM system presented best results, by using statistics tools, we investigated the mechanism controlling the rate release of the model drug, from tablets made with this new matrix. As a final result we concluded that the best combination of polysaccharides was achieved with MSG and Xanthan Gum, with mass ratio of 1:2, using glutharaldehyde aqueous solution as cross-linking agent. It presented a prevalent zero order kinetics, which is a very important feature when thinking about an extended-release oral dosage.O objetivo deste trabalho foi o desenvolvimento de novos sistemas de matrizes hidrofílicas através da formação de ligações cruzadas (cross-linking entre a Goma da Semente da Algaroba (GSA, uma galactomanana que ocorre no endosperma das sementes de uma árvore nativa do Brasil, a Prosopis juliflora DC, e dois polissacarídeos bem conhecidos pela sua habilidade de retardar a libera

  16. The dialogically extended mind

    DEFF Research Database (Denmark)

    Fusaroli, Riccardo; Gangopadhyay, Nivedita; Tylén, Kristian

    2014-01-01

    A growing conceptual and empirical literature is advancing the idea that language extends our cognitive skills. One of the most influential positions holds that language – qua material symbols – facilitates individual thought processes by virtue of its material properties. Extending upon this model......, we argue that language enhances our cognitive capabilities in a much more radical way: The skilful engagement of public material symbols facilitates evolutionarily unprecedented modes of collective perception, action and reasoning (interpersonal synergies) creating dialogically extended minds. We...... relate our approach to other ideas about collective minds and review a number of empirical studies to identify the mechanisms enabling the constitution of interpersonal cognitive systems....

  17. The Extended Enterprise concept

    DEFF Research Database (Denmark)

    Larsen, Lars Bjørn; Vesterager, Johan; Gobbi, Chiara

    1999-01-01

    This paper provides an overview of the work that has been done regarding the Extended Enterprise concept in the Common Concept team of Globeman 21 including references to results deliverables concerning the development of the Extended Enterprise concept. The first section presents the basic concept...... picture from Globeman21, which illustrates the Globeman21 way of realising the Extended Enterprise concept. The second section presents the Globeman21 EE concept in a life cycle perspective, which to a large extent is based on the thoughts and ideas behind GERAM (ISO/DIS 15704)....

  18. 艾司西酞普兰文立法辛缓释剂治疗抑郁症的比较研究%A clinical observation of escitalopram and venlafaxine-extended-release (XR) general in the treatment of outpatients with depression

    Institute of Scientific and Technical Information of China (English)

    王鹤秋; 任志斌; 王素珍

    2011-01-01

    To observe and compare the efficacy and safety of escitalopram and venlafax-ine-extended-release (XR) in the treatment of outpatients with depression. METHODS; 89 outpatients with depression were randomized to receive escitalopram or venlafaxine-extended-re-lease (XR) for 8 weeks, and dose titrated from 10 mg/d or 75 mg/d to a maximum of 20 mg/d or 150 mg/d respectively within the first 2 weeks of treatment. Effects and adverse events were e-valuated with MADRS, HAMA, CGI and TESS before and after the treatment. RESULTS; After 8 weeks treatment, total scores of MADRS of 39 patients with escitalopram or 36 venlafaxine-XRboth showed significant change compared with baseline, and escitalopram. After 8 weeks treatment, percentage of recovery were 51. 28% and 44.44% respectively, while significant improvement percentage were 71.79% and 61.11% in each group. CONCLUSION; Escitalopram and venlafaxine-extended-release (XR) both are effective and safe antidepressants, and escitalopram has a faster and better effectiveness profile in treatment of depression.%目的:评价和比较艾司西酞普兰与文拉法辛缓释剂治疗抑郁症的临床疗效和安全性.方法:将89例门诊抑郁症患者分别随机给予艾司西酞普兰和文拉法辛缓释剂治疗,在2周内逐步增高剂量至20 mg/d或150 mg/d,在治疗前后用蒙格马利—阿斯伯格抑郁评定量表(MADRS)、临床整体印象改善评分( CGI)和副反应量表(TESS)评定疗效和不良反应.结果:43例门诊抑郁症患者应用艾司西酞普兰,46例患者应用文拉法辛缓释剂,经治疗后MADRS的总分较治疗前均有统计学差异,第1周时艾司西酞普兰与文拉法辛缓释剂临床缓解率和有效率比较有统计学差异(P<0.01),治疗第8周时艾司西酞普兰与文拉法辛缓释剂临床缓解率分别是51.28%、44.44%;有效率为71.79%、61.11%;两组不良反应轻且发生率少.结论:艾司西酞普兰与文拉法辛缓释剂均能安全、有

  19. Rational extended thermodynamics

    CERN Document Server

    Müller, Ingo

    1998-01-01

    Ordinary thermodynamics provides reliable results when the thermodynamic fields are smooth, in the sense that there are no steep gradients and no rapid changes. In fluids and gases this is the domain of the equations of Navier-Stokes and Fourier. Extended thermodynamics becomes relevant for rapidly varying and strongly inhomogeneous processes. Thus the propagation of high­ frequency waves, and the shape of shock waves, and the regression of small-scale fluctuation are governed by extended thermodynamics. The field equations of ordinary thermodynamics are parabolic while extended thermodynamics is governed by hyperbolic systems. The main ingredients of extended thermodynamics are • field equations of balance type, • constitutive quantities depending on the present local state and • entropy as a concave function of the state variables. This set of assumptions leads to first order quasi-linear symmetric hyperbolic systems of field equations; it guarantees the well-posedness of initial value problems and f...

  20. Symmetric Extended Ockham Algebras

    Institute of Scientific and Technical Information of China (English)

    T.S. Blyth; Jie Fang

    2003-01-01

    The variety eO of extended Ockham algebras consists of those algealgebra with an additional endomorphism k such that the unary operations f and k commute. Here, we consider the cO-algebras which have a property of symmetry. We show that there are thirty two non-isomorphic subdirectly irreducible symmetric extended MS-algebras and give a complete description of them.2000 Mathematics Subject Classification: 06D15, 06D30

  1. Collaborative Proposal to Extend ONR YIP Research with BRC Efforts

    Science.gov (United States)

    2013-09-30

    DISTRIBUTION STATEMENT: Approved for public release; distribution is unlimited. Collaborative Proposal to Extend ONR YIP research with BRC Efforts...SEP 2013 2. REPORT TYPE 3. DATES COVERED 00-00-2013 to 00-00-2013 4. TITLE AND SUBTITLE Collaborative Proposal to Extend ONR YIP research with

  2. Extended spider cognition.

    Science.gov (United States)

    Japyassú, Hilton F; Laland, Kevin N

    2017-05-01

    There is a tension between the conception of cognition as a central nervous system (CNS) process and a view of cognition as extending towards the body or the contiguous environment. The centralised conception requires large or complex nervous systems to cope with complex environments. Conversely, the extended conception involves the outsourcing of information processing to the body or environment, thus making fewer demands on the processing power of the CNS. The evolution of extended cognition should be particularly favoured among small, generalist predators such as spiders, and here, we review the literature to evaluate the fit of empirical data with these contrasting models of cognition. Spiders do not seem to be cognitively limited, displaying a large diversity of learning processes, from habituation to contextual learning, including a sense of numerosity. To tease apart the central from the extended cognition, we apply the mutual manipulability criterion, testing the existence of reciprocal causal links between the putative elements of the system. We conclude that the web threads and configurations are integral parts of the cognitive systems. The extension of cognition to the web helps to explain some puzzling features of spider behaviour and seems to promote evolvability within the group, enhancing innovation through cognitive connectivity to variable habitat features. Graded changes in relative brain size could also be explained by outsourcing information processing to environmental features. More generally, niche-constructed structures emerge as prime candidates for extending animal cognition, generating the selective pressures that help to shape the evolving cognitive system.

  3. An extended day program

    Directory of Open Access Journals (Sweden)

    Ševkušić-Mandić Slavica G.

    2002-01-01

    Full Text Available The paper presents the results of a pilot project evaluation, carried out as an action investigation whose aim was to provide a better quality extended day for primary school students. The project included the training of teachers involved in extended day program, designing of special activities performed by teachers with children once a week as well as changes and equipping of premises where children stay. The aims of the program were conception and performance of activities in a less formal way than during regular instructional days, linking of learning at school and acquired knowledge to everyday experiences, and work on contents contributing to the development of child's interests and creativity. The program was accomplished in a Belgrade primary school during the 2001/2002 academic year, comprising students of 1st and 2nd grades (N=77. The effects of the program were monitored throughout the academic year (observation and teachers' reports on accomplished workshops and at the end of the academic year (teachers and students' opinions of the program, academic achievement and creativity of students attending the extended day program compared with students not attending it. Findings about positive effects of the program on students' broadening of interests and willingness to express themselves creatively, indicate unequivocally that there is a need for developing special extended day programs. The extended day program is an opportunity for school to exert greater educational influence that has yet to be tapped.

  4. Effects of fluvastatin extended release tablets on the intermediate lesions of patients with coronary artery disease evaluated by virtual histology-intravascular ultrasound%虚拟组织学-血管内超声观察氟伐他汀缓释片对冠状动脉临界病变的影响

    Institute of Scientific and Technical Information of China (English)

    杨海波; 赵晓燕; 赵荫涛; 张金盈; 李凌

    2012-01-01

    Objective To obserrve the effect of fluvastatin extended release tablets on the intermediate lesions of patients with coronmy artery disease evaluated by virtual histology-intravascular ultrasound(VH-IVUS).Methods Forty-three patients with intermediate lesions of acute coronary syndrome (ACS) were examined by coronary angiography (CAG) and VH-IVUS,the target vessel diameter stenosis (DS) were analyzed using quantitative coronary angiography (QCA).The plaque burden,minimal luman area(MLA) and composition variation were analyzed using VH-IVUS.All selected patients were treated with 80 mg fluvastatin extended release tablets for 6 months.The serum lipid levels of patients before and after the treatment were compared.After 6 months the reexamination of the vessel by CAG and VH-IVUS were performed.Results After 6 months,the TC,LDL-C and TG levels were significantly decreased,while the HDL-C level was significantly increased (P < 0.05).The VH-IVUS analysis showed that the proportion of necrosis core was decreased from (22.6 ± 7.5) % to (15.1 ± 7.1) %(P < 0.05) and the proportion of fibrous tissue was increased from (44.4 ± 9.7) % to (51.2 ± 9.9) %(P < 0.05).There has no significant change in DS,the plaque burden,MLA,the proportion of dense calcium or fibro-fatty tissue.Conclusions The treatment of fluvastatin for 6 months might stable plaque and prevent the progression of atherosclerosis in patients with intermediate coronary artery lesions.%目的 应用虚拟组织学-血管内超声(VH-IVUS)观察氟伐他汀缓释片对冠状动脉临界病变患者斑块进展及其成分的影响.方法 选择经冠状动脉造影(CAG)和VH-IVUS检查无需介入治疗的冠状动脉临界病变患者43例,给予氟伐他汀缓释片(80 mg)治疗6个月后复查CAG及VH-IVUS,比较治疗前后血脂、定量冠状动脉造影(QCA)分析目标血管段直径狭窄率(DS)变化,VH-IVUS分析斑块负荷、最小管腔面积(MLA)、斑块成分变化.结果

  5. 舌下含服硝苯地平缓释片联合卡托普利治疗高血压急症的疗效评价%Efficacy of Sublingual Extended Release Nifedipine Tablets and Captopril Tablets for Treatment of Hypertensive Crisis

    Institute of Scientific and Technical Information of China (English)

    王载芳; 谢跃伟

    2016-01-01

    Objective:To assess the antihypertensive effects of single use of extended release nifedipine(NFP) tablets or Captopril(CTP) tablets and combination of these two drugs .Methods:135 cases of patients with hypertensive Crisis were randomly divided into three group ,each comprised 45 of them .The groups of patients received sublingual NFP or CTP alone served as control group ,with the groups of patients received both NFP and CTP as observation groups .Ob‐serve the changes of blood pressure (systolic blood pressure and diastolic blood pressure) and heart rate at the time be‐fore injection and 5 minutes ,10 minutes ,30 minutes ,1 hour ,2 hours ,4 hours ,6 hours ,8 hours after administration .Re‐sults:In NFP group ,the blood pressure significantly dropped 5minutes after oral ,and reached and maintained the maxi‐mal peak 1 hour after oral ,the total efficacy was 77 .8% ;in CTP group ,the blood pressure significantly dropped 4minutes after oral ,and reached and maintained the maximal peak 1~2 hours after oral ,the total efficacy was 84 .4% ;in the combined use of NFP and CTP group ,the blood pressure significantly dropped 5 minutes after oral ,and reached and maintained the maximal peak 30 minutes~2 hours after oral ,the total efficacy was 93 .3% .Three groups of heart rate has no obvious change(P>0 .05) .The combined use of NFP and CTP produced better effect in decreasing blood pressure than the sole use of NFP or CTP(P<0 .05) .Conclusion:Sublingual extended release NFP tablets and CTP tablets can get ideal antihypertensive effects in time for patients with hypertensive crisis .%目的:评价舌下含服硝苯地平缓释片联合卡托普利治疗高血压急症的降压疗效。方法:将我院收治的高血压急症患者135例随机分成3组,其中舌下含服硝苯地平缓释片组45例,舌下含服卡托普利片45例,同时含服硝苯地平缓释片、卡托普利片45例,观察三组用药前后血压、心率的变化。结果:硝

  6. Extending Critical Performativity

    DEFF Research Database (Denmark)

    Spicer, André; Alvesson, Mats; Kärreman, Dan

    2016-01-01

    In this article we extend the debate about critical performativity. We begin by outlining the basic tenets of critical performativity and how this has been applied in the study of management and organization. We then address recent critiques of critical performance. We note these arguments suffer...... from an undue focus on intra-academic debates; engage in author-itarian theoretical policing; feign relevance through symbolic radicalism; and repackage common sense. We take these critiques as an opportunity to offer an extended model of critical performativity that involves focusing on issues...

  7. Quantification of Niacin and Its Metabolite Nicotinuric Acid in Human Plasma by LC-MS/MS: Application to a Clinical Trial of a Fixed Dose Combination Tablet of Niacin Extended-Release/Simvastatin (500 mg/10 mg in Healthy Chinese Volunteers

    Directory of Open Access Journals (Sweden)

    Pingping Zhang

    2015-01-01

    Full Text Available Our paper aimed to develop rapid, sensitive, and specific LC-MS/MS method for the quantification of niacin (NA and its metabolite nicotinuric acid (NUA in human plasma. Following protein precipitation with acetonitrile, the NA, NUA, and internal standard (5-fluorouracil were separated on a Zorbax 300SB-C8 column (250 mm × 4.6 mm, 5 μm with a mobile phase consisting of methanol-2 mM ammonium acetate (3 : 97, v/v at a flow rate of 1 mL/min (split 1 : 1. A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated in negative ion mode. The linear concentration ranges of the calibration curves were 5–800 ng/mL for NA and NUA. The intra-assay RSD for quality control (QC samples were from 5.0% to 8.7% for NA, and 5.5% to 7.6% for NUA. The interassay RSD for QC samples were from 2.8% to 9.4% for NA, and 3.7% to 5.8% for NUA. The relative errors for QC samples were from −2.2% to 2.3% for NA, and −0.6% to 3.2% for NUA. The method was successfully applied to the investigation of the pharmacokinetic profiles of NA, NUA in human after single dose administration of Niacin extended-release/Simvastatin tablet (500 mg/10 mg.

  8. 美托洛尔缓释片治疗左室射血分数保留的心力衰竭的疗效观察%Metoprolol extended-release tablets in treatment of heart failure with preserved ejection fraction

    Institute of Scientific and Technical Information of China (English)

    谢赟; 蒋金法

    2012-01-01

    Objective To evaluate the efficacy of metoprolol extended-release tablets in treatment of heart failure with preserved ejection fraction (HFpEF). Methods One hundred and thirty three patients with HFpEF were randomly assigned to receive conventional therapy and metoprolol extended-release tablets (metoprolol group, n = 69) or receive conventional therapy only ( control group, n = 64). The blood pressure, heart rate, left ventricular diastolic function were compared between the two groups. The metoprolol group was further divided into low-dosage treated group[ (47. 5 ±10) mg/d, n =40] and high-dosage group [ (95 ±20) mg/d, n - 29 ]. Results Left ventricular ejection fraction (LVEF) , left ventricular end diastolic diameter(LVEDD), blood pressure, heart rate and N-terminal pro-brain natriuretic peptide ( NT-pro-BNP) levels were improved significantly 12 months after treatment in the metoprolol group, there were significantly differences between metoprolol and control groups(P < 0. 05, P < 0. 01). The isovolumic relaxation time (IVRT) , early left ventricular filling velocity(E), velocity of left ventricular filling contributed by atrial contraction (A) , E/A and left atrial diameter( LAD) after treatment were better than those before treatments ( P < 0. 01), and also better than those in control group (P <0.01). Compared to those in low-dosage group,heart rate and plasma NTproBNP concentration in high-dosage group were significantly improved (P < 0. 01). Conclusion Metoprolol extended-release tablets can improve the heart diastolic function in patients with HFpEF; and high-dosage metoprolol may inhibit the over-activation of neural hormones and further improves biological efficacy.%目的 观察美托洛尔缓释片对左室射血分数保留的心力衰竭(heart failure with preserved ejection fraction,HFpEF)患者心功能的改善作用.方法 入选HFpEF患者133例,随机分成美托洛尔缓释片治疗组69例及对照组64例,两组患者均给予抗心力

  9. Analyzing Living Surveys: Visualization Beyond the Data Release

    NARCIS (Netherlands)

    Buddelmeijer, H.; Noorishad, P.; Williams, D.; Ivanova, M.; Roerdink, J. B. T. M.; Valentijn, E. A.

    2015-01-01

    Surveys need to provide more than periodic data releases. Science often requires data that is not captured in such releases. This mismatch between the constraints set by a fixed data release and the needs of the scientists is solved in the Astro-WISE information system by extending its request-drive

  10. Analyzing Living Surveys : Visualization Beyond the Data Release

    NARCIS (Netherlands)

    Buddelmeijer, H.; Noorishad, P.; Williams, D.; Ivanova, M.; Roerdink, J. B. T. M.; Valentijn, E. A.; Taylor, A.R.; Rosolowski, E.

    2015-01-01

    Surveys need to provide more than periodic data releases. Science often requires data that is not captured in such releases. This mismatch between the constraints set by a fixed data release and the needs of the scientists is solved in the Astro-WISE information system by extending its request-drive

  11. Parameterization of extended systems

    DEFF Research Database (Denmark)

    Niemann, Hans Henrik

    2006-01-01

    The YJBK parameterization (of all stabilizing controllers) is extended to handle systems with additional sensors and/or actuators. It is shown that the closed loop transfer function is still an affine function in the YJBK parameters in the nominal case. Further, some closed-loop stability results...

  12. Observation on therapeutic effects of fluvoxamine combined with cognitive behavior therapy in the treatment of obsessive compulsive disorder%氟伏沙明联合认知行为疗法治疗强迫症的疗效观察

    Institute of Scientific and Technical Information of China (English)

    谢志强; 邓勤香; 凌瀚; 邓友梅; 焦志欢; 谭常赞

    2012-01-01

    Objective To discuss the clinical curative effect of fluvoxamine combined with cognitive behavior therapy in the treatment of obsessive compulsive disorder.Methods In 12 weeks,60 cases with cognitive behavior received fluvoxamine combined with cognitive therapy,the other 60 cases received only fluvoxamine therapy.Observation indexes included comparative observation of treatment for the Obsessive Compulsive Scale,self consistency and Congruence Scale score and clinical curative effect after 4 weeks,8 weeks and 12 weeks.Results After 12 weeks of treatment,the effect rate was 90% in the study group and 73.3% in the control group with significant differences (P<0.05).After the treatment,the Yale-Brown Obsessive Compulsive Scale and self consistency and Congruence Scale score were decreased significantly (P<0.01) in two groups,and the study group decreased more significantly than those in the control group (P<0.01).There was no significant difference in adverse reaction of two groups (P>0.05).Conclusion In the treatment of obsessive compulsive disorder,fluvoxamine combined with cognitive behavior therapy provides effect more significantly than that with fluvoxamine.%目的 探讨氟伏沙明联合认知行为疗法治疗强迫症的临床疗效.方法 将120例强迫症患者随机分为研究组(氟伏沙明联合认知行为疗法)和对照组(单用氟伏沙明治疗),每组各60例,疗程12周,观察比较治疗4周,8周,12周后强迫量表、自我和谐量表评分情况及临床疗效.结果 研究组治疗12周后有效率90%,对照组有效率73.3%,差异有显著性(P<0.05).治疗后两组Yale-Brown强迫量表和自我和谐量表评分均较治疗前显著下降(P<0.01),同期研究组均较对照组下降更显著(P<0.01),两组副反应差异无显著性(P>0.05).结论 氟伏沙明联合认知行为疗法治疗强迫症疗效更显著,优于单用氟伏沙明治疗.

  13. THE EXTENDED VIRGO CLUSTER CATALOG

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Suk; Rey, Soo-Chang; Lee, Youngdae; Chung, Jiwon; Pak, Mina; Yi, Wonhyeong; Lee, Woong [Department of Astronomy and Space Science, Chungnam National University, 99 Daehak-ro, Daejeon 305-764 (Korea, Republic of); Jerjen, Helmut [Research School of Astronomy and Astrophysics, The Australian National University, Cotter Road, Weston, ACT 2611 (Australia); Lisker, Thorsten [Astronomisches Rechen-Institut, Zentrum für Astronomie der Universität Heidelberg (ZAH), Mönchhofstraße 12-14, D-69120 Heidelberg (Germany); Sung, Eon-Chang [Korea Astronomy and Space Science institute, 776 Daedeokdae-ro, Daejeon 305-348 (Korea, Republic of)

    2015-01-01

    We present a new catalog of galaxies in the wider region of the Virgo cluster, based on the Sloan Digital Sky Survey (SDSS) Data Release 7. The Extended Virgo Cluster Catalog (EVCC) covers an area of 725 deg{sup 2} or 60.1 Mpc{sup 2}. It is 5.2 times larger than the footprint of the classical Virgo Cluster Catalog (VCC) and reaches out to 3.5 times the virial radius of the Virgo cluster. We selected 1324 spectroscopically targeted galaxies with radial velocities less than 3000 km s{sup –1}. In addition, 265 galaxies that have been overlooked in the SDSS spectroscopic survey but have available redshifts in the NASA Extragalactic Database are also included. Our selection process secured a total of 1589 galaxies, 676 of which are not included in the VCC. The certain and possible cluster members are defined by means of redshift comparison with a cluster infall model. We employed two independent and complementary galaxy classification schemes: the traditional morphological classification based on the visual inspection of optical images and a characterization of galaxies from their spectroscopic features. SDSS u, g, r, i, and z passband photometry of all EVCC galaxies was performed using Source Extractor. We compare the EVCC galaxies with the VCC in terms of morphology, spatial distribution, and luminosity function. The EVCC defines a comprehensive galaxy sample covering a wider range in galaxy density that is significantly different from the inner region of the Virgo cluster. It will be the foundation for forthcoming galaxy evolution studies in the extended Virgo cluster region, complementing ongoing and planned Virgo cluster surveys at various wavelengths.

  14. Extended Irreversible Thermodynamics

    CERN Document Server

    Jou, David

    2010-01-01

    This is the 4th edition of the highly acclaimed monograph on Extended Irreversible Thermodynamics, a theory that goes beyond the classical theory of irreversible processes. In contrast to the classical approach, the basic variables describing the system are complemented by non-equilibrium quantities. The claims made for extended thermodynamics are confirmed by the kinetic theory of gases and statistical mechanics. The book covers a wide spectrum of applications, and also contains a thorough discussion of the foundations and the scope of the current theories on non-equilibrium thermodynamics. For this new edition, the authors critically revised existing material while taking into account the most recent developments in fast moving fields such as heat transport in micro- and nanosystems or fast solidification fronts in materials sciences. Several fundamental chapters have been revisited emphasizing physics and applications over mathematical derivations. Also, fundamental questions on the definition of non-equil...

  15. Introduction to Extended Electrodynamics

    CERN Document Server

    Donev, S

    1997-01-01

    This paper summarizes the motivations and results obtained so far in the frame of a particular non-linearization of Classical Electrodynamics, which was called Extended Electrodynamics. The main purpose pursued with this non-linear extension of the classical Maxwell's equations is to have a reliable field-theoretical approach in describing (3+1) soliton-like electromagnetic formations, in particular, to build an extended and finite field model of free photons and photon complexes. The first chapter gives a corresponding analysis of Maxwell theory and introduces the new equations. The second chapter gives a full account of the results, including the photon-like solutions, in the vacuum case. A new concept, called scale factor, is defined and successfully used. Two ways for describing the intrinsic angular momentum are given. Interference of two photon-like solutions is also considered. The third chapter considers interaction with external fields (continuous media) on the base of establishing correspondence bet...

  16. Extended Theories of Gravitation

    Directory of Open Access Journals (Sweden)

    Fatibene Lorenzo

    2013-09-01

    Full Text Available Within the framework of extended theories of gravitation we shall discuss physical equivalences among different formalisms and classical tests. As suggested by the Ehlers-Pirani-Schild framework, the conformal invariance will be preserved and its effect on observational protocols discussed. Accordingly, we shall review standard tests showing how Palatini f(R-theories naturally passes solar system tests. Observation protocols will be discussed in this wider framework.

  17. Extended Ensemble Monte Carlo

    OpenAIRE

    Iba, Yukito

    2000-01-01

    ``Extended Ensemble Monte Carlo''is a generic term that indicates a set of algorithms which are now popular in a variety of fields in physics and statistical information processing. Exchange Monte Carlo (Metropolis-Coupled Chain, Parallel Tempering), Simulated Tempering (Expanded Ensemble Monte Carlo), and Multicanonical Monte Carlo (Adaptive Umbrella Sampling) are typical members of this family. Here we give a cross-disciplinary survey of these algorithms with special emphasis on the great f...

  18. Propelling Extended Objects

    Science.gov (United States)

    Humbert, Richard

    2010-01-01

    A force acting on just part of an extended object (either a solid or a volume of a liquid) can cause all of it to move. That motion is due to the transmission of the force through the object by its material. This paper discusses how the force is distributed to all of the object by a gradient of stress or pressure in it, which creates the local…

  19. The Fly Printer - Extended

    DEFF Research Database (Denmark)

    Beloff, Laura; Klaus, Malena

    2016-01-01

    Artist talk / Work-in-progress What is the purpose of a machine or an artifact, like the Fly Printer, that is dislocated, that produces images that have no meaning, no instrumentality, that depict nothing in the world? The biological and the cultural are reunited in this apparatus as a possibilit...... the results. The extended version of the Fly Printer containing the technological perception and DNNs is a collaboration between Laura Beloff and Malene Theres Klaus...

  20. extendFromReads

    Energy Technology Data Exchange (ETDEWEB)

    2013-10-03

    This package assists in genome assembly. extendFromReads takes as input a set of Illumina (eg, MiSeq) DNA sequencing reads, a query seed sequence and a direction to extend the seed. The algorithm collects all seed--]matching reads (flipping reverse--]orientation hits), trims off the seed and additional sequence in the other direction, sorts the remaining sequences alphabetically, and prints them aligned without gaps from the point of seed trimming. This produces a visual display distinguishing the flanks of multi-]copy seeds. A companion script hitMates.pl collects the mates of seed--]hi]ng reads, whose alignment reveals longer extensions from the seed. The collect/trim/sort strategy was made iterative and scaled up in the script denovo.pl, for de novo contig assembly. An index is pre--]built using indexReads.pl that for each unique 21--]mer found in all the reads, records its gfateh of extension (whether extendable, blocked by low coverage, or blocked by branching after a duplicated sequence) and other characteristics. Importantly, denovo.pl records all branchings that follow a branching contig endpoint, providing contig-]extension information

  1. Extended recombinant bacterial ghost system.

    Science.gov (United States)

    Lubitz, W; Witte, A; Eko, F O; Kamal, M; Jechlinger, W; Brand, E; Marchart, J; Haidinger, W; Huter, V; Felnerova, D; Stralis-Alves, N; Lechleitner, S; Melzer, H; Szostak, M P; Resch, S; Mader, H; Kuen, B; Mayr, B; Mayrhofer, P; Geretschläger, R; Haslberger, A; Hensel, A

    1999-08-20

    Controlled expression of cloned PhiX174 gene E in Gram-negative bacteria results in lysis of the bacteria by formation of an E-specific transmembrane tunnel structure built through the cell envelope complex. Bacterial ghosts from a variety of bacteria are used as non-living candidate vaccines. In the recombinant ghost system, foreign proteins are attached on the inside of the inner membrane as fusions with specific anchor sequences. Ghosts have a sealed periplasmic space and the export of proteins into this space vastly extends the capacity of ghosts or recombinant ghosts to function as carriers of foreign antigens. In addition, S-layer proteins forming shell-like self assembly structures can be expressed in candidate vaccine strains prior to E-mediated lysis. Such recombinant S-layer proteins carrying foreign epitopes further extend the possibilities of ghosts as carriers of foreign epitopes. As ghosts have inherent adjuvant properties, they can be used as adjuvants in combination with subunit vaccines. Subunits or other ligands can also be coupled to matrixes like dextran which are used to fill the internal lumen of ghosts. Oral, aerogenic or parenteral immunization of experimental animals with recombinant ghosts induced specific humoral and cellular immune responses against bacterial and target components including protective mucosal immunity. The most relevant advantage of recombinant bacterial ghosts as immunogens is that no inactivation procedures that denature relevant immunogenic determinants are employed in this production. This fact explains the superior quality of ghosts when compared to other inactivated vaccines. The endotoxic component of the outer membrane does not limit the use of ghosts as vaccine candidates but triggers the release of several potent immunoregulatory cytokines. As carriers, there is no limitation in the size of foreign antigens that can be inserted in the membrane and the capacity of all spaces including the membranes, peri

  2. Inequalities of extended beta and extended hypergeometric functions.

    Science.gov (United States)

    Mondal, Saiful R

    2017-01-01

    We study the log-convexity of the extended beta functions. As a consequence, we establish Turán-type inequalities. The monotonicity, log-convexity, log-concavity of extended hypergeometric functions are deduced by using the inequalities on extended beta functions. The particular cases of those results also give the Turán-type inequalities for extended confluent and extended Gaussian hypergeometric functions. Some reverses of Turán-type inequalities are also derived.

  3. News/Press Releases

    Data.gov (United States)

    Office of Personnel Management — A press release, news release, media release, press statement is written communication directed at members of the news media for the purpose of announcing programs...

  4. A multicenter, primary-care-based, open-label study to assess the success of converting opioid-experienced patients with chronic moderate-to-severe pain to morphine sulfate and naltrexone hydrochloride extended-release capsules using a standardized conversion guide

    Directory of Open Access Journals (Sweden)

    Setnik B

    2015-07-01

    Full Text Available Beatrice Setnik,1 Carl L Roland,1 Kenneth W Sommerville,1,2 Glenn C Pixton,1 Robert Berke,3,4 Anne Calkins,5 Veeraindar Goli1,2 1Pfizer Inc, 2Duke University Medical Center, Durham, NC, USA; 3Family Health Medical Services PLLC, Mayville, 4Department of Social and Preventive Medicine, State University of New York at Buffalo, Buffalo, 5New York Spine & Wellness Center, Syracuse, NY, USA Objective: To evaluate the conversion of opioid-experienced patients with chronic moderate-to-severe pain to extended-release morphine sulfate with sequestered naltrexone hydrochloride (MSN using a standardized conversion guide. Methods: This open-label, single-arm study was conducted in 157 primary care centers in the United States. A total of 684 opioid-experienced adults with chronic moderate-to-severe pain were converted to oral administration of MSN from transdermal fentanyl and oral formulations of hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and other morphine products using a standardized conversion guide. The primary endpoint was the percentage of patients achieving a stable MSN dose within a 6-week titration phase. Secondary endpoints included duration of time to stable dose, number of titration steps, safety and efficacy measures, and investigator assessment of conversion guide utility. Results: Of the 684 patients, 51.3% were converted to a stable dose of MSN (95% confidence interval: 47.5%, 55.1%. The mean (standard deviation number of days to stable dose was 20 (8.94, and number of titration steps to stable dose was 2.4 (1.37. The majority of adverse events were mild/moderate and consistent with opioid therapy. Mean pain scores at stable dose decreased from baseline. Investigators were generally satisfied with the conversion guide and, in 94% of cases, reported they would use it again. Conclusion: Conversion to MSN treatment using the standardized MSN conversion guide was an attainable goal in approximately half of the population of

  5. Extended Testability Analysis Tool

    Science.gov (United States)

    Melcher, Kevin; Maul, William A.; Fulton, Christopher

    2012-01-01

    The Extended Testability Analysis (ETA) Tool is a software application that supports fault management (FM) by performing testability analyses on the fault propagation model of a given system. Fault management includes the prevention of faults through robust design margins and quality assurance methods, or the mitigation of system failures. Fault management requires an understanding of the system design and operation, potential failure mechanisms within the system, and the propagation of those potential failures through the system. The purpose of the ETA Tool software is to process the testability analysis results from a commercial software program called TEAMS Designer in order to provide a detailed set of diagnostic assessment reports. The ETA Tool is a command-line process with several user-selectable report output options. The ETA Tool also extends the COTS testability analysis and enables variation studies with sensor sensitivity impacts on system diagnostics and component isolation using a single testability output. The ETA Tool can also provide extended analyses from a single set of testability output files. The following analysis reports are available to the user: (1) the Detectability Report provides a breakdown of how each tested failure mode was detected, (2) the Test Utilization Report identifies all the failure modes that each test detects, (3) the Failure Mode Isolation Report demonstrates the system s ability to discriminate between failure modes, (4) the Component Isolation Report demonstrates the system s ability to discriminate between failure modes relative to the components containing the failure modes, (5) the Sensor Sensor Sensitivity Analysis Report shows the diagnostic impact due to loss of sensor information, and (6) the Effect Mapping Report identifies failure modes that result in specified system-level effects.

  6. Extended associative memories

    OpenAIRE

    J.H Sossa Azuela; R. Barrón Fernández

    2007-01-01

    The #945; #946; associative memories recently developed in Ref 10 have proven to be powerful tools for memorizing and recalling patterns when they appear distorted by noise. However they are only useful in the binary case. In this paper we show that it is possible to extend these memories now to the gray-level case. To get the desired extension, we take the original operators #945; and #946;, foundation of the #945; #946; memories, and propose a more general family of operators. We find t...

  7. Branes in extended spacetime

    CERN Document Server

    Sakatani, Yuho

    2016-01-01

    We propose a novel approach to the brane worldvolume theory based on the geometry of extended field theories; double field theory and exceptional field theory. We demonstrate the effectiveness of this approach by showing that one can reproduce the conventional bosonic string/membrane actions, and the M5-brane action in the weak field approximation. At a glance, the proposed 5-brane action without approximation looks different from the known M5-brane actions, but it is consistent with the known non-linear self-duality relation, and it may provide a new formulation of a single M5-brane action. Actions for exotic branes are also discussed.

  8. Extending the MINLO method

    CERN Document Server

    Frederix, Rikkert

    2015-01-01

    We consider improving POWHEG+MINLO simulations, so as to also render them NLO accurate in the description of observables receiving contributions from events with lower parton multiplicity than present in their underlying NLO calculation. On a conceptual level we follow the strategy of the so-called MINLO' programs. Whereas the existing MINLO' framework requires explicit analytic input from higher order resummation, here we derive an effective numerical approximation to these ingredients, by imposing unitarity. This offers a way of extending the MINLO' method to more complex processes, complementary to the known route which uses explicit computations of high-accuracy resummation inputs. Specifically, we have focused on Higgs-plus-two-jet production (HJJ) and related processes. We also consider how one can cover three units of multiplicity at NLO accuracy, i.e. we consider how the HJJ-MINLO simulation may yield NLO accuracy for inclusive H, HJ, and HJJ quantities. We perform a feasibility study assessing the po...

  9. Extending juvenility in grasses

    Energy Technology Data Exchange (ETDEWEB)

    Kaeppler, Shawn; de Leon Gatti, Natalia; Foerster, Jillian

    2017-04-11

    The present invention relates to compositions and methods for modulating the juvenile to adult developmental growth transition in plants, such as grasses (e.g. maize). In particular, the invention provides methods for enhancing agronomic properties in plants by modulating expression of GRMZM2G362718, GRMZM2G096016, or homologs thereof. Modulation of expression of one or more additional genes which affect juvenile to adult developmental growth transition such as Glossy15 or Cg1, in conjunction with such modulation of expression is also contemplated. Nucleic acid constructs for down-regulation of GRMZM2G362718 and/or GRMZM2G096016 are also contemplated, as are transgenic plants and products produced there from, that demonstrate altered, such as extended juvenile growth, and display associated phenotypes such as enhanced yield, improved digestibility, and increased disease resistance. Plants described herein may be used, for example, as improved forage or feed crops or in biofuel production.

  10. Extended Theories of Gravity

    CERN Document Server

    Capozziello, Salvatore

    2011-01-01

    Extended Theories of Gravity can be considered a new paradigm to cure shortcomings of General Relativity at infrared and ultraviolet scales. They are an approach that, by preserving the undoubtedly positive results of Einstein's Theory, is aimed to address conceptual and experimental problems recently emerged in Astrophysics, Cosmology and High Energy Physics. In particular, the goal is to encompass, in a self-consistent scheme, problems like Inflation, Dark Energy, Dark Matter, Large Scale Structure and, first of all, to give at least an effective description of Quantum Gravity. We review the basic principles that any gravitational theory has to follow. The geometrical interpretation is discussed in a broad perspective in order to highlight the basic assumptions of General Relativity and its possible extensions in the general framework of gauge theories. Principles of such modifications are presented, focusing on specific classes of theories like f (R)-gravity and scalar-tensor gravity in the metric and Pala...

  11. Extending over time

    DEFF Research Database (Denmark)

    Christensen, Tanya Karoli; Jensen, Torben Juel; Christensen, Marie Herget

    Studies of general extenders (GEs), such as Eng. and stuff like that, or something, typically find that it is a feature of youth speech, sometimes correlated with sex and class (e.g. Dubois 1992, Stubbe and Holmes 1995, Cheshire 2007, Tagliamonte and Denis 2010, Pichler and Levey 2011), but only...... that variants with sådan noget, though prevalent across the board, may be stigmatized, since they are produced mainly by young WC males, and exhibit an overall drop in frequency over time. In our paper, we will use GEs in Danish as a case study for evaluating prevailing assumptions about the relationship...... few have a design enabling them to distinguish unequivocally between age grading and communal change. In this paper, we present the results of a large-scale study of GEs in Danish, based on Copenhagen data from the LANCHART corpus, encompassing speech from three age cohorts, of which two have been...

  12. Extended Poisson Exponential Distribution

    Directory of Open Access Journals (Sweden)

    Anum Fatima

    2015-09-01

    Full Text Available A new mixture of Modified Exponential (ME and Poisson distribution has been introduced in this paper. Taking the Maximum of Modified Exponential random variable when the sample size follows a zero truncated Poisson distribution we have derived the new distribution, named as Extended Poisson Exponential distribution. This distribution possesses increasing and decreasing failure rates. The Poisson-Exponential, Modified Exponential and Exponential distributions are special cases of this distribution. We have also investigated some mathematical properties of the distribution along with Information entropies and Order statistics of the distribution. The estimation of parameters has been obtained using the Maximum Likelihood Estimation procedure. Finally we have illustrated a real data application of our distribution.

  13. Extended Ewald summation technique

    Science.gov (United States)

    Kylänpää, Ilkka; Räsänen, Esa

    2016-09-01

    We present a technique to improve the accuracy and to reduce the computational labor in the calculation of long-range interactions in systems with periodic boundary conditions. We extend the well-known Ewald method by using a linear combination of screening Gaussian charge distributions instead of only one. This enables us to find faster converging real-space and reciprocal space summations. The combined simplicity and efficiency of our method is demonstrated, and the scheme is readily applicable to large-scale periodic simulations, classical as well as quantum. Moreover, apart from the required a priori optimization the method is straightforward to include in most routines based on the Ewald method within, e.g., density-functional, molecular dynamics, and quantum Monte Carlo calculations.

  14. Stars with Extended Atmospheres

    Science.gov (United States)

    Sterken, C.

    2002-12-01

    This Workshop consisted of a full-day meeting of the Working Group "Sterren met Uitgebreide Atmosferen" (SUA, Working Group Stars with Extended Atmospheres), a discussion group founded in 1979 by Kees de Jager, Karel van der Hucht and Pik Sin The. This loose association of astronomers and astronomy students working in the Dutch-speaking part of the Low Countries (The Netherlands and Flanders) organised at regular intervals one-day meetings at the Universities of Utrecht, Leiden, Amsterdam and Brussels. These meetings consisted of the presentation of scientific results by junior as well as senior members of the group, and by discussions between the participants. As such, the SUA meetings became a forum for the exchange of ideas, and for asking questions and advice in an informal atmosphere. Kees de Jager has been chairman of the WG SUA from the beginning in 1979 till today, as the leading source of inspiration. At the occasion of Prof. Kees de Jager's 80th birthday, we decided to collect the presented talks in written form as a Festschrift in honour of this well-respected and much beloved scientist, teacher and friend. The first three papers deal with the personality of Kees de Jager, more specifically with his role as a supervisor and mentor of young researchers and as a catalyst in the research work of his colleagues. And also about his remarkable role in the establishment of astronomy education and research at the University of Brussels. The next presentation is a very detailed review of solar research, a field in which Cees was prominently active for many years. Then follow several papers dealing with stars about which Kees is a true expert: massive stars and extended atmospheres.

  15. Beyond six parameters: extending $\\Lambda$CDM

    CERN Document Server

    Di Valentino, Eleonora; Silk, Joseph

    2015-01-01

    Cosmological constraints are usually derived under the assumption of a $6$ parameters $\\Lambda$-CDM theoretical framework or simple one-parameter extensions. In this paper we present, for the first time, cosmological constraints in a significantly extended scenario, varying up to $12$ cosmological parameters simultaneously, including the sum of neutrino masses, the neutrino effective number, the dark energy equation of state, the gravitational waves background and the running of the spectral index of primordial perturbations. Using the latest Planck 2015 data release (with polarization) we found no significant indication for extensions to the standard $\\Lambda$-CDM scenario, with the notable exception of the angular power spectrum lensing amplitude, $A_{\\rm lens}$ that is larger than the expected value at more than two standard deviations even when combining the Planck data with BAO and supernovae type Ia external datasets. In our extended cosmological framework, we find that a combined Planck+BAO analysis co...

  16. Can Asymmetry of Solar Activity be Extended into Extended Cycle?

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    With the use of the Royal Greenwich Observatory data set of sunspot groups, an attempt is made to examine the north-south asymmetry of solar activity in the "extended" solar cycles. It is inferred that the asymmetry established for individual solar cycles does not extend to the "extended" cycles.

  17. Release of RANKERN 16A

    Directory of Open Access Journals (Sweden)

    Bird Adam

    2017-01-01

    Full Text Available RANKERN 16 is the latest version of the point-kernel gamma radiation transport Monte Carlo code from AMEC Foster Wheeler’s ANSWERS Software Service. RANKERN is well established in the UK shielding community for radiation shielding and dosimetry assessments. Many important developments have been made available to users in this latest release of RANKERN. The existing general 3D geometry capability has been extended to include import of CAD files in the IGES format providing efficient full CAD modelling capability without geometric approximation. Import of tetrahedral mesh and polygon surface formats has also been provided. An efficient voxel geometry type has been added suitable for representing CT data. There have been numerous input syntax enhancements and an extended actinide gamma source library. This paper describes some of the new features and compares the performance of the new geometry capabilities.

  18. Release of RANKERN 16A

    Science.gov (United States)

    Bird, Adam; Murphy, Christophe; Dobson, Geoff

    2017-09-01

    RANKERN 16 is the latest version of the point-kernel gamma radiation transport Monte Carlo code from AMEC Foster Wheeler's ANSWERS Software Service. RANKERN is well established in the UK shielding community for radiation shielding and dosimetry assessments. Many important developments have been made available to users in this latest release of RANKERN. The existing general 3D geometry capability has been extended to include import of CAD files in the IGES format providing efficient full CAD modelling capability without geometric approximation. Import of tetrahedral mesh and polygon surface formats has also been provided. An efficient voxel geometry type has been added suitable for representing CT data. There have been numerous input syntax enhancements and an extended actinide gamma source library. This paper describes some of the new features and compares the performance of the new geometry capabilities.

  19. 急性期精神分裂症转换帕利哌酮治疗的疗效及安全性%Efficacy and safety of paliperidone extended-release tablets as substituting medication in acute patients with schizophrenia

    Institute of Scientific and Technical Information of China (English)

    许本健; 陈菊凤

    2012-01-01

    目的:对接受足疗程奥氮平单一治疗无效的急性期精神分裂症住院患者,逐步替换为帕利哌酮缓释片单一治疗后,观察其疗效和不良反应,以及对患者个人和社会功能的改善作用.方法:将45例受试者随机分为两组,研究组23例,由原先的奥氮平替换为帕利哌酮缓释片治疗6周;对照组22例,由原先的奥氮平替换为利培酮治疗6周.治疗前后分别用阳性与阴性症状量表(PANSS)、个人与社会功能量表(PSP)和不良反应量表(TESS)评价疗效和不良反应.结果:研究组PANSS总分、阳性症状分、阴性症状分和一般精神病理分自基线降低,以及PSP总分自基线升高均具有统计学意义(P<0.01).研究组发生失眠、嗜睡、锥体外系不良反应(EPS)、血清催乳素升高各1例,但均可耐受.结论:对于奥氮平治疗无效的急性期精神分裂症患者,替换为帕利哌酮缓释片治疗或能安全有效地控制阳性/阴性症状,且明显改善患者的个人和社会功能.%AIM: To evaluate the efficacy, safety and effect on personal and social function of paliperidone extended-release tablets (paliper-idone ER) as substitution in inpatients experiencing an acute episode of schizophrenia, and unresponsive to prior medications of olanzapine be-sids. METHODS: Forty-five patients enrolled were assigned to receive paliperidone ER or ris-peridone for 6 weeks, meanwhile their prior medications of olanzapine were slowly tapered off within first 2 weeks. Positive and Negative Symptom Scale (PANSS) was used to assess the efficacy, Personal and Social Performance Scale (PSP) for social function, Treatment Emergent Symptom Scale (TESS) for tolerability and safety. RESULTS-PANSS total and PANSS factors scores significantly decreased from baseline to end point in paliperidone ER treatment group (P<0. 01), moreover, significant improvements in mean PSP scale scores were observed (P

  20. Control study of paliperidone extended - release tablet and ziprasidone on the cognitive function and quality of life of patients with schizophrenia%帕利哌酮缓释片和齐拉西酮对精神分裂症患者认知功能和生活质量影响的对照研究

    Institute of Scientific and Technical Information of China (English)

    范洪峰

    2015-01-01

    Objective To explore the influence of paliperidone and ziprasidone on the cognitive function and quality of life in pa-tients with schizophrenia. Methods 96 cases of schizophrenia patients conform to the International classification of diseases tenth edi-tion(ICD - 10)were randomly divided into paliperidone group(observation group,48 cases)and ziprasidone capsule group(control group,48 cases)by using the random number table method. Two groups of patients were assessed by Wisconsin Card Sorting Test (WCST),Continuous Performance Test(CPT)to evaluate cognitive function and using WHO Quality of Life - BREF(WHOQOL -BREF)to evaluate quality of life before and after 8 weeks of treatment. Results The scores of the number of correct response and per-sistent error number of WCST in observation group improved was statistically significant than control group after 8 weeks treatment(t =2. 294,t = 2. 049,P < 0. 05). The scores of the CPT2 and CPT3 in observation group improved was statistically significant than control group(t = 2. 242,P < 0. 05;t = 2. 671,P < 0. 01). The scores of the field of physiological,psychological and social relationship of WHOQOL - BREF in observation group improved was statistically significant than control group(t = 2. 465,2. 166,2. 444,P < 0. 05). Conclusion Paliperidone extended - release tablet can be effectively to improve the cognitive function and quality of life in patients with schizophrenia was better than ziprasidone.%目的:探讨帕利哌酮与齐拉西酮对精神分裂症患者认知功能和生活质量的影响。方法采用随机数字表法将符合《国际疾病分类(第10版)》(ICD -10)精神分裂症诊断标准的96例精神分裂症患者分为帕利哌酮缓释片组(观察组)和齐拉西酮胶囊组(对照组)各48例,分别于治疗前和治疗8周后采用威斯康星卡片分类测验(WCST)和持续操作测验(CPT)测评认知功能,采用世界卫生

  1. 盐酸哌甲酯控释剂治疗注意缺陷多动障碍儿童疗效分析%Curative effect of methylphenidate extended-release tablets ( OROS MPH ) in treating different clinical type of attention deficit hyperactivity disorder( ADHD)

    Institute of Scientific and Technical Information of China (English)

    刘文龙; 江瑞芬; 王真真; 张娟

    2012-01-01

    Objective To analyze the curative effect and side effect of methylphenidate extended-release tablets ( OROS MPH) in treating different clinical type of attention deficit hyperactivity disorder ( ADHD). Methods Fifty children diagnosed with ADHD participated in a self-controlled clinical trial. All the patients took OROS MPH for 4 weeks. The primary efficacy measurement was SNAP-IV Rating Scale. Results The improvement of the children with different ADHD sub-type was distinctive after treatment. The overall response rate was 80. 00% and the complete remission rate was 40. 00% . The response rate of attention deficit type children was significantly higher than that of other two subtypes (P<0. 05). The common side effects were anorexia and nausea. The incidence rate of side effect had no significant difference among different clinical type of attention deficit hyperactivity disorder (ADHD). Conclusion OROS MPH is an operative medicine to cure ADHD, especially for attention deficit type children. The incidence rate of side effect of different clinical type is no significant difference.%目的 分析盐酸哌甲酯控释剂(专注达)治疗不同临床亚型注意缺陷多动障碍(ADHD)的疗效及副作用发生情况,为其在临床的应用提供借鉴.方法 采用自身前后对照设计,收集临床确诊并使用专注达的ADHD儿童50例,应用SNAP-Ⅳ量表分别于用药前及用药后4周评价疗效,同时收集出现的副作用情况.结果 用药后,不同临床亚型ADHD患儿症状改善明显,总体有效率为80.00%,总体缓解率为40.00%.注意缺陷为主型与其他2种亚型治疗有效率差异有统计学意义(P<0.05).常见副作用为食欲下降和恶心,不同临床亚型副作用的发生率差异无统计学意义(P>0.05).结论 专注达是治疗注意缺陷多动障碍的有效药物,对注意缺陷为主型疗效尤其显著.不同临床亚型副作用的发生无差别.

  2. Extended chameleon models

    Science.gov (United States)

    Brax, Philippe; Tamanini, Nicola

    2016-05-01

    We extend the chameleon models by considering scalar-fluid theories where the coupling between matter and the scalar field can be represented by a quadratic effective potential with density-dependent minimum and mass. In this context, we study the effects of the scalar field on Solar System tests of gravity and show that models passing these stringent constraints can still induce large modifications of Newton's law on galactic scales. On these scales we analyze models which could lead to a percent deviation of Newton's law outside the virial radius. We then model the dark matter halo as a Navarro-Frenk-White profile and explicitly find that the fifth force can give large contributions around the galactic core in a particular model where the scalar field mass is constant and the minimum of its potential varies linearly with the matter density. At cosmological distances, we find that this model does not alter the growth of large scale structures and therefore would be best tested on galactic scales, where interesting signatures might arise in the galaxy rotation curves.

  3. Chirally extended quantum chromodynamics

    CERN Document Server

    Brower, R C; Tan, C I; Richard C Brower; Yue Shen; Chung-I Tan

    1994-01-01

    We propose an extended Quantum Chromodynamics (XQCD) Lagrangian in which the fermions are coupled to elementary scalar %\\sigma and \\pi fields through a Yukawa coupling which preserves chiral invariance. Our principle motivation is to find a new lattice formulation for QCD which avoids the source of critical slowing down usually encountered as the bare quark mass is tuned to the chiral limit. The phase diagram and the weak coupling limit for XQCD are studied. They suggest a conjecture that the continuum limit of XQCD is the same as the continuum limit of conventional lattice formulation of QCD. As examples of such universality, we present the large N solutions of two prototype models for XQCD, in which the mass of the spurious pion and sigma resonance go to infinity with the cut-off. Even if the universality conjecture turns out to be false, we believe that XQCD will still be useful as a low energy effective action for QCD phenomenology on the lattice. Numerical simulations are recommended to further investiga...

  4. On the extended loop calculus

    CERN Document Server

    Griego, J R

    1995-01-01

    Some features of extended loops are considered. In particular, the behaviour under diffeomorphism transformations of the wavefunctions with support on the extended loop space are studied. The basis of a method to obtain analytical expressions of diffeomorphism invariants via extended loops are settled. Applications to knot theory and quantum gravity are considered.

  5. Extended Mixed Vector Equilibrium Problems

    Directory of Open Access Journals (Sweden)

    Mijanur Rahaman

    2014-01-01

    Full Text Available We study extended mixed vector equilibrium problems, namely, extended weak mixed vector equilibrium problem and extended strong mixed vector equilibrium problem in Hausdorff topological vector spaces. Using generalized KKM-Fan theorem (Ben-El-Mechaiekh et al.; 2005, some existence results for both problems are proved in noncompact domain.

  6. Market Diffusion of Extended Cycle Hormonal Contraceptives

    Directory of Open Access Journals (Sweden)

    Megen Leeds Schumacher, Pharm.D.

    2012-01-01

    Full Text Available Background: Extended cycle hormonal contraceptives (e.g. Seasonale, Seasonique when introduced in 2003 were considered a very novel approach to contraception. The idea of manipulating the menstrual cycle so that women would experience just four menstruations a year was radical and was assumed to be responsible for the slow acceptance rate among the general public.Objective: This report analyzes two different aspects of the acceptance of this unique idea in the population. The first was the level of usage of extended cycle hormonal contraceptives in the general population, which was measured by a review of sales figures over time in the United States. The second was an examination of market diffusion as it relates to consumer perceptions regarding the characteristics of these products.Methods: To determine the degree of usage of extended cycle hormonal contraceptives the yearly sales, in terms of units sold, were compared with that of other leading methods of hormonal contraception. Along with the data, survey answers were obtained from 65 women who volunteered to participate in the study. Participants were selected randomly to represent the target population to assess the level of awareness about the benefits, risks, and any other concerns regarding the use of extended cycle hormonal contraceptives.Results: The yearly sales data of units sold showed a definitive increase in the sales of extended cycle hormonal contraceptives since their release on the market. The survey results showed an overwhelming awareness in the study population about the extended regimen. However, only about half of the women in the survey group were aware of its benefits. The main concern reported was the perceived significant side effect profile.Conclusion: Though awareness about the extended cycle hormonal contraception regimen was widespread, the survey population was not well informed about the advantages and the disadvantages regarding the degree of severity of side

  7. Extended propagation model for interfacial crack in composite material structure

    Institute of Scientific and Technical Information of China (English)

    闫相桥; 冯希金

    2002-01-01

    An interfacial crack is a common damage in a composite material structure . An extended propaga-tion model has been established for an interfacial crack to study the dependence of crack growth on the relativesizes of energy release rates at left and right crack tips and the properties of interfacial material characterize thegrowth of interfacial crack better.

  8. TOLLAN-XICOCOTITLAN: A RECONSTRUCTED CITY BY AUGMENTED REALITY (EXTENDED

    Directory of Open Access Journals (Sweden)

    M. en C. Martha Rosa Cordero López

    2014-10-01

    Full Text Available Work In Terminal presents the analysis, design, implementation and results of Reconstruction Xicocotitlan Tollan-through augmented reality (Extended, which will release information about the Toltec capital supplemented by presenting an overview of the main premises of the Xicocotitlan Tollan city supported dimensional models based on the augmented reality technique showing the user a virtual representation of buildings in Tollan phase.

  9. RECONSTRUCTION OF TOLLANXICOCOTITLAN CITY BY AUGMENTED REALITY (EXTENDED

    Directory of Open Access Journals (Sweden)

    M. en C. Martha Rosa Cordero Lopez

    2014-05-01

    Full Text Available Work In Terminal presents the analysis, design, implementation and results of Reconstruction Xicocotitlan Tollan-through augmented reality (Extended, which will release information about the Toltec capital supplemented by presenting an overview of the main premises of the Xicocotitlan Tollan city supported dimensional models based on the augmented reality technique showing the user a virtual representation of buildings in Tollan phase.

  10. Toxics Release Inventory (TRI)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) is a dataset compiled by the U.S. Environmental Protection Agency (EPA). It contains information on the release and waste...

  11. ELECTROMAGNETIC RELEASE MECHANISM

    Science.gov (United States)

    Michelson, C.

    1960-09-13

    An electromagnetic release mechanism is offered that may be used, for example, for supporting a safety rod for a nuclear reactor. The release mechanism is designed to have a large excess holding force and a rapid, uniform, and dependable release. The fast release is accomplished by providing the electromagnet with slotttd polts separated by an insulating potting resin, and by constructing the poles with a ferro-nickel alloy. The combination of these two features materially reduces the eddy current power density whenever the magnetic field changes during a release operation. In addition to these features, the design of the armature is such as to provide ready entrance of fluid into any void that might tend to form during release of the armature. This also improves the release time for the mechanism. The large holding force for the mechanism is accomplished by providing a small, selected, uniform air gap between the inner pole piece and the armature.

  12. On core stability and extendability

    OpenAIRE

    Shellshear, Evan

    2007-01-01

    This paper investigates conditions under which the core of a TU cooperative game is stable. In particular the author extends the idea of extendability to find new conditions under which the core is stable. It is also shown that these new conditions are not necessary for core stability.

  13. On core stability and extendability

    OpenAIRE

    Shellshear, Evan

    2007-01-01

    This paper investigates conditions under which the core of a TU cooperative game is stable. In particular the author extends the idea of extendability to find new conditions under which the core is stable. It is also shown that these new conditions are not necessary for core stability.

  14. Extended Active Disturbance Rejection Controller

    Science.gov (United States)

    Gao, Zhiqiang (Inventor); Tian, Gang (Inventor)

    2016-01-01

    Multiple designs, systems, methods and processes for controlling a system or plant using an extended active disturbance rejection control (ADRC) based controller are presented. The extended ADRC controller accepts sensor information from the plant. The sensor information is used in conjunction with an extended state observer in combination with a predictor that estimates and predicts the current state of the plant and a co-joined estimate of the system disturbances and system dynamics. The extended state observer estimates and predictions are used in conjunction with a control law that generates an input to the system based in part on the extended state observer estimates and predictions as well as a desired trajectory for the plant to follow.

  15. Release the Body, Release the Mind.

    Science.gov (United States)

    Stoner, Martha Goff

    1998-01-01

    A college English teacher describes the anxiety and resentment of students during in-class writing assignments and the successful classroom use of meditation and body movement. Movement seemed to relax the students, change their attitudes, and release their creative impulses to write. Implications related to the body-mind connection are pondered.…

  16. Quantum Mechanics of Extended Objects

    CERN Document Server

    Sastry, R R

    2000-01-01

    We propose a quantum mechanics of extended objects that accounts for the finite extent of a particle defined via its Compton wavelength. The Hilbert space representation theory of such a quantum mechanics is presented and this representation is used to demonstrate the quantization of spacetime. The quantum mechanics of extended objects is then applied to two paradigm examples, the fuzzy (extended object) harmonic oscillator and the Yukawa potential. In the second example the phenomenological coupling constant of the $\\omega$ meson which mediates the short range and repulsive nucleon force as well as the repulsive core radius are theoretically predicted.

  17. Extended scaling in high dimensions

    Science.gov (United States)

    Berche, B.; Chatelain, C.; Dhall, C.; Kenna, R.; Low, R.; Walter, J.-C.

    2008-11-01

    We apply and test the recently proposed 'extended scaling' scheme in an analysis of the magnetic susceptibility of Ising systems above the upper critical dimension. The data are obtained by Monte Carlo simulations using both the conventional Wolff cluster algorithm and the Prokof'ev-Svistunov worm algorithm. As already observed for other models, extended scaling is shown to extend the high-temperature critical scaling regime over a range of temperatures much wider than that achieved conventionally. It allows for an accurate determination of leading and sub-leading scaling indices, critical temperatures and amplitudes of the confluent corrections.

  18. Cosmological dynamics of extended chameleons

    CERN Document Server

    Tamanini, Nicola

    2016-01-01

    We investigate the cosmological dynamics of the recently proposed extended chameleon models at both background and linear perturbation levels. Dynamical systems techniques are employed to fully characterize the evolution of the universe at the largest distances, while structure formation is analysed at sub-horizon scales within the quasi-static approximation. The late time dynamical transition from dark matter to dark energy domination can be well described by almost all extended chameleon models considered, with no deviations from $\\Lambda$CDM results at both background and perturbation levels. The results obtained in this work confirm the cosmological viability of extended chameleons as alternative dark energy models.

  19. Effect of fluvoxamine treatment on cognitive bias to the emotional facial information in social phobia%氟伏沙明对社交恐惧症患者情绪图片信息认知偏倚的影响

    Institute of Scientific and Technical Information of China (English)

    姚建军; 张紫娟

    2012-01-01

    目的 探讨氟伏沙明对社交恐惧症患者情绪图片信息认知偏倚的影响.方法 选择符合CCMD-3社交恐惧症诊断标准的26例患者作为实验组,与实验组性别、年龄匹配的26例健康人作为对照组.实验组予氟伏沙明治疗8周.两组分别在治疗前以及8周后予情绪图片刺激的点探测任务检测,比较治疗前以及8周后反应时以及注意偏向分差别.结果 实验组8周后HAMA明显低于治疗前(P<0.05).重复测量ANOVA显示,探测位置主效应显著,异侧位置的反应时长于同侧位置(P<0.05);情绪面孔图片类型与组间水平交互作用显著(P<0.05);探测位置与组间水平交互作用显著(P<0.05);情绪面孔图片类型与探测位置交互作用显著(P<0.05);情绪面孔图片类型×探测位置×组间水平交互作用显著(P<0.05),1sD比较显示实验组对恐惧面孔图片异侧位置的反应时长于同侧位置(P<0.05).实验组治疗8周后对恐惧面孔图片反应时以及注意偏向分明显低于治疗前(均P< 0.05).结论 社交恐惧症患者对恐惧面孔图片信息表现出认知偏倚,氟伏沙明具有改善认知偏倚的作用.%Objective To investigate the effect of fluvoxamine treatment on cognitive bias to the e-motional facial information in patients with social phobia(SP). Methods 26 patients met CCMD—3 criteria for SP were enrolled as research group and marched sexual and age 26 healthy persons enrolled as control group. Patients were treated with fluvoxamine for 8weeks. All participants measured with Dot-probe task of Emotional facial information at base and after 8 weeks. RTs and attentional bias scores were compared respectively. Results After 8 weeks, HAMA scores in research group were lower than that of at base (P RTs of antarafacial site were longer than that of homonymy site. It revealed a significant probe site and group interaction (P < 0. 05), a significant Emotional facial information type and

  20. Cognitive Transformations and Extended Expertise

    Science.gov (United States)

    Menary, Richard; Kirchhoff, Michael

    2014-01-01

    Expertise is extended by becoming immersed in cultural practices. We look at an example of mathematical expertise in which immersion in cognitive practices results in the transformation of expert performance.

  1. Extended gcd of quadratic integers

    CERN Document Server

    Miled, Abdelwaheb

    2010-01-01

    Computation of the extended g