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Drugs in R&D 2010In March 2010, Orexigen(R) Therapeutics submitted a new drug application (NDA) for approval of naltrexone sustained release (SR)/bupropion SR (Contrave(R)) for the... (Review)
Review
In March 2010, Orexigen(R) Therapeutics submitted a new drug application (NDA) for approval of naltrexone sustained release (SR)/bupropion SR (Contrave(R)) for the treatment of obesity in the US. The tablet contains naltrexone SR 32 mg and bupropion SR 360 mg. The drug has been tested in four randomized, double-blind, placebo-controlled, phase III trials and the co-primary endpoints were met in each case. This review discusses the key development milestones and clinical trial program to date.
Topics: Animals; Anti-Obesity Agents; Bupropion; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Drug Combinations; Drug Evaluation, Preclinical; Drugs, Investigational; Humans; Naltrexone; Obesity
PubMed: 20509712
DOI: 10.2165/11537710-000000000-00000 -
Canadian Family Physician Medecin de... Oct 2021An adolescent who smokes regularly came to my clinic for help quitting. While I am aware that bupropion is a first-line medication for smoking cessation among adults, is...
QUESTION
An adolescent who smokes regularly came to my clinic for help quitting. While I am aware that bupropion is a first-line medication for smoking cessation among adults, is it effective and safe for adolescents?
ANSWER
Most adolescent smokers in Canada would like to quit, but more than 90% of the attempts are unsuccessful. Bupropion appears to be more effective than other pharmacologic options in improving abstinence among adolescents who smoke in the short term; however, it is not approved by Health Canada for those younger than 18 years. Bupropion has not been associated with an increase in adverse events in smoking cessation trials. More research is needed on the long-term effectiveness and safety of bupropion in this population.
Topics: Adolescent; Adult; Benzazepines; Bupropion; Humans; Nicotinic Agonists; Quinoxalines; Smoking Cessation; Varenicline
PubMed: 34649897
DOI: 10.46747/cfp.6710743 -
Drug Metabolism Letters 2019Bupropion (BUP) is widely used as an antidepressant and smoking cessation aid. There are three major pharmacologically active metabolites of BUP, Erythrohydrobupropion...
BACKGROUND
Bupropion (BUP) is widely used as an antidepressant and smoking cessation aid. There are three major pharmacologically active metabolites of BUP, Erythrohydrobupropion (EB), Hydroxybupropion (OHB) and Threohydrobupropion (TB). At present, the mechanisms underlying the overall disposition and systemic clearance of BUP and its metabolites have not been well understood, and the role of transporters has not been studied.
OBJECTIVE
The goal of this study was to investigate whether BUP and its active metabolites are substrates of the major hepatic uptake and efflux transporters.
METHOD
CHO or HEK293 cell lines or plasma membrane vesicles that overexpress OATP1B1, OATP1B3, OATP2B1, OATP4A1, OCT1, BCRP, MRP2 or P-gp were used in cellular or vesicle uptake and inhibition assays. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) was used to quantify transport activity.
RESULTS
BUP and its major active metabolites were actively transported into the CHO or HEK293 cells overexpressing OATP1B1, OATP1B3 or OATP2B1; however, such cellular active uptake could not be inhibited at all by prototypical inhibitors of any of the OATP transporters. These compounds were not transported by OCT1, BCRP, MRP2 or P-gp either. These results suggest that the major known hepatic transporters likely play a minor role in the overall disposition and systemic clearance of BUP and its active metabolites in humans. We also demonstrated that BUP and its metabolites were not transported by OATP4A1, an uptake transporter on the apical membrane of placental syncytiotrophoblasts, suggesting that OATP4A1 is not responsible for the transfer of BUP and its metabolites from the maternal blood to the fetal compartment across the placental barrier in pregnant women.
CONCLUSION
BUP and metabolites are not substrates of the major hepatic transporters tested and thus these hepatic transporters likely do not play a role in the overall disposition of the drug. Our results also suggest that caution should be taken when using the model CHO and HEK293 cell lines to evaluate potential roles of transporters in drug disposition.
Topics: Animals; Antidepressive Agents, Second-Generation; Bupropion; CHO Cells; Cricetulus; HEK293 Cells; Humans; Membrane Transport Proteins; Metabolic Clearance Rate; Smoking Cessation Agents
PubMed: 30488806
DOI: 10.2174/1872312813666181129101507 -
Einstein (Sao Paulo, Brazil) 2022To evaluate the effects of combining topiramate, bupropion and naltrexone in obesity-induced rats on their weight and subcutaneous adipose tissue.
OBJECTIVE
To evaluate the effects of combining topiramate, bupropion and naltrexone in obesity-induced rats on their weight and subcutaneous adipose tissue.
METHODS
A total of 40 male Wistar rats were induced to obesity for 8 weeks and the animals were divided into 8 groups: Ctr - control, G0 - Sham, G1 - oral saline solution (1.0mL/day), G2 - topiramate (20.0mg/kg) and bupropion (5.0mg/kg), G3 - naltrexone (20.0mg/kg), G4 - topiramate (20.0mg/kg), G5 - bupropion (5.0mg/kg) and G6 - topiramate (20.0mg/kg), bupropion (5.0mg/kg) and naltrexone (20.0mg/kg). During the experiment, all animals were weighed weekly. After 30 days of treatment animals were euthanized and their skin fragments were processed and stained with hematoxylin and eosin for morphological, morphometric and biochemical analyzes.
RESULTS
The only group that presented a decrease in the volume of subcutaneous adipose tissue was G3, but this decrease was not significant when compared with the other groups. The G4, the G5 and the G6 presented increased adipose tissue volume. Data showed that until the eighth week all animals increased their weight by approximately 50%. After treatment animals of all groups, except G3, increased their weight from 4% to 9% approximately. The G3 was the only group that lost weight, but this decrease was not significant.
CONCLUSION
The medicines studied were not efficient in reducing weight in obese rats. However, it should be considered that 30-day treatment period is not enough to observe the stronger effects of these drugs.
Topics: Animals; Bupropion; Humans; Male; Naltrexone; Obesity; Rats; Rats, Wistar; Subcutaneous Fat; Topiramate
PubMed: 35649051
DOI: 10.31744/einstein_journal/2022AO5587 -
Journal of Clinical PsychopharmacologyThere has long been a clinical belief that bupropion exacerbates anxiety. The purpose of the current retrospective study is to compare anxiety severity over time in...
PURPOSE/BACKGROUND
There has long been a clinical belief that bupropion exacerbates anxiety. The purpose of the current retrospective study is to compare anxiety severity over time in those prescribed selective serotonin reuptake inhibitors (SSRIs) versus bupropion.
METHODS/PROCEDURES
Archival data (N = 8457) from patients receiving psychiatric care from a national tele-mental health company were used. Propensity matching was used to create SSRI and bupropion groups using 17 covariates. These samples were then compared using repeated measures analysis of variance on Generalized Anxiety Disorder Scale 7 scores at start of treatment, 6 weeks, and 12 weeks.
FINDINGS/RESULTS
The SSRI and bupropion groups were significantly different across a number of variables. In the entire sample, the bupropion group had significantly greater anxiety levels. However, for propensity-matched comparisons, there were no significant interactions between group and time (ie, groups did not differ and improved comparably over time).
IMPLICATIONS/CONCLUSIONS
Using propensity matching, there were no differences in anxiety outcome between those prescribed selective serotonin reuptake inhibitor versus bupropion across 12 weeks of treatment.
Topics: Humans; Bupropion; Retrospective Studies; Depressive Disorder, Major; Selective Serotonin Reuptake Inhibitors; Anxiety
PubMed: 36706284
DOI: 10.1097/JCP.0000000000001658 -
The American Journal of Geriatric... Oct 2016There is a relative paucity of information on both empirical and subjective treatment strategies for treatment-resistant depression (TRD), especially in late life. This...
BACKGROUND
There is a relative paucity of information on both empirical and subjective treatment strategies for treatment-resistant depression (TRD), especially in late life. This paper reviews the findings from two 2016 surveys conducted through the American Psychiatric Association publication the Psychiatric Times and via a member survey by the American Association for Geriatric Psychiatry (AAGP).
METHODS
We present the results of the two surveys in terms of descriptive frequencies and percentages and discuss the strengths and weaknesses of various approaches to late-life TRD.
RESULTS
The Psychiatric Times survey received 468 responses, and the AAGP survey received 117 responses, giving an overall sample of 585 responses. The majority (76.3%) of respondents from both groups believed that a large randomized study comparing the risks and benefits of augmentation and switching strategies for TRD in patients aged 60 years and older would be helpful, and 80% of clinicians believed their practice would benefit from the findings of such a study. Of the treatment strategies that need evidence of efficacy, the most popular options were augmentation/combination strategies, particularly augmentation with aripiprazole (58.7%), bupropion (55.0%), and lithium (50.9%).
CONCLUSIONS
Late-life TRD constitutes a large proportion of clinical practices, particularly of geriatric psychiatry, with lacking evidence of efficacy of most treatment strategies. These surveys indicate a clear need for a large randomized study that compares risks and benefits of augmentation and switching strategies.
Topics: Aged; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Attitude of Health Personnel; Bupropion; Depressive Disorder, Treatment-Resistant; Drug Therapy, Combination; Female; Humans; Lithium Compounds; Male; Middle Aged; Psychiatry; Surveys and Questionnaires
PubMed: 27591914
DOI: 10.1016/j.jagp.2016.05.010 -
Drug Metabolism and Disposition: the... Nov 2016Bupropion sustained release is used to promote smoking cessation in males and nonpregnant females. However, its efficacy as a smoking cessation aid during pregnancy is...
Bupropion sustained release is used to promote smoking cessation in males and nonpregnant females. However, its efficacy as a smoking cessation aid during pregnancy is not reported. The pregnancy-associated changes in maternal physiology may alter the pharmacokinetics and pharmacodynamics of bupropion and consequently its efficacy in pregnant smokers. Therefore, the aims of this study were to determine the steady-state pharmacokinetics of bupropion during pregnancy and the effect of functional genetic variants of CYP2B6 and CYP2C19 on bupropion pharmacokinetics in pregnant women. Plasma and urine concentrations of bupropion and its metabolites hydroxybupropion (OHBUP), threohydrobupropion, and erythrohydrobupropion were determined by liquid chromatography-mass spectrometry. Subjects were genotyped for five nonsynonymous single-nucleotide polymorphisms that result in seven CYP2B6 alleles, namely *2, *3, *4, *5, *6, *7, and *9, and for CYP2C19 variants *2, *3, and *17 The present study reports that the isoform-specific effect of pregnancy on bupropion-metabolizing enzymes along with the increase of renal elimination of the drug could collectively result in a slight decrease in exposure to bupropion in pregnancy. In contrast, pregnancy-induced increase in CYP2B6-catalyzed bupropion hydroxylation did not impact the plasma levels of OHBUP, probably due to a higher rate of OHBUP glucuronidation, and renal elimination associated with pregnancy. Therefore, exposure to OHBUP, a pharmacologically active metabolite of the bupropion, appears to be similar to that of the nonpregnant state. The predicted metabolic phenotypes of CYP2B6*6 and variant alleles of CYP2C19 in pregnancy are similar to those in the nonpregnant state.
Topics: Adult; Alleles; Antidepressive Agents, Second-Generation; Bupropion; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Female; Humans; Polymorphism, Single Nucleotide; Pregnancy; Prospective Studies; Young Adult
PubMed: 27528039
DOI: 10.1124/dmd.116.071530 -
British Journal of Clinical Pharmacology Feb 2014Strategies for assisting smoking cessation include behavioural counselling to enhance motivation and to support attempts to quit and pharmacological intervention to... (Review)
Review
Strategies for assisting smoking cessation include behavioural counselling to enhance motivation and to support attempts to quit and pharmacological intervention to reduce nicotine reinforcement and withdrawal from nicotine. Three drugs are currently used as first line pharmacotherapy for smoking cessation, nicotine replacement therapy, bupropion and varenicline. Compared with placebo, the drug effect varies from 2.27 (95% CI 2.02, 2.55) for varenicline, 1.69 (95% CI 1.53, 1.85) for bupropion and 1.60 (95% CI 1.53, 1.68) for any form of nicotine replacement therapy. Despite some controversy regarding the safety of bupropion and varenicline, regulatory agencies consider these drugs as having a favourable benefit/risk profile. However, given the high rate of psychiatric comorbidity in dependent smokers, practitioners should closely monitor patients for neuropsychiatric symptoms. Second-line pharmacotherapies include nortriptyline and clonidine. This review also offers an overview of pipeline developments and issues related to smoking cessation in special populations such as persons with psychiatric comorbidity and pregnant and adolescent smokers.
Topics: Adolescent; Benzazepines; Bupropion; Counseling; Drug Design; Female; Humans; Molecular Sequence Data; Pregnancy; Quinoxalines; Smoking Cessation; Tobacco Use Cessation Devices; Tobacco Use Disorder; Varenicline
PubMed: 23488726
DOI: 10.1111/bcp.12116 -
The Journal of Pharmacology and... Aug 2016Bupropion, widely used as an antidepressant and smoking cessation aid, undergoes complex metabolism to yield numerous metabolites with unique disposition, effect, and... (Clinical Trial)
Clinical Trial
Bupropion, widely used as an antidepressant and smoking cessation aid, undergoes complex metabolism to yield numerous metabolites with unique disposition, effect, and drug-drug interactions (DDIs) in humans. The stereoselective plasma and urinary pharmacokinetics of bupropion and its metabolites were evaluated to understand their potential contributions to bupropion effects. Healthy human volunteers (n = 15) were administered a single oral dose of racemic bupropion (100 mg), which was followed by collection of plasma and urine samples and determination of bupropion and metabolite concentrations using novel liquid chromatography-tandem mass spectrometry assays. Time-dependent, elimination rate-limited, stereoselective pharmacokinetics were observed for all bupropion metabolites. Area under the plasma concentration-time curve from zero to infinity ratios were on average approximately 65, 6, 6, and 4 and Cmax ratios were approximately 35, 6, 3, and 0.5 for (2R,3R)-/(2S,3S)-hydroxybupropion, R-/S-bupropion, (1S,2R)-/(1R,2S)-erythrohydrobupropion, and (1R,2R)-/(1S,2S)-threohydrobupropion, respectively. The R-/S-bupropion and (1R,2R)-/(1S,2S)-threohydrobupropion ratios are likely indicative of higher presystemic metabolism of S- versus R-bupropion by carbonyl reductases. Interestingly, the apparent renal clearance of (2S,3S)-hydroxybupropion was almost 10-fold higher than that of (2R,3R)-hydroxybupropion. The prediction of steady-state pharmacokinetics demonstrated differential stereospecific accumulation [partial area under the plasma concentration-time curve after the final simulated bupropion dose (300-312 hours) from 185 to 37,447 nM⋅h] and elimination [terminal half-life of approximately 7-46 hours] of bupropion metabolites, which may explain observed stereoselective differences in bupropion effect and DDI risk with CYP2D6 at steady state. Further elucidation of bupropion and metabolite disposition suggests that bupropion is not a reliable in vivo marker of CYP2B6 activity. In summary, to our knowledge, this is the first comprehensive report to provide novel insight into mechanisms underlying bupropion disposition by detailing the stereoselective pharmacokinetics of individual bupropion metabolites, which will enhance clinical understanding of bupropion's effects and DDIs with CYP2D6.
Topics: Adult; Aged; Bupropion; Female; Healthy Volunteers; Humans; Male; Middle Aged; Stereoisomerism; Young Adult
PubMed: 27255113
DOI: 10.1124/jpet.116.232876 -
The Primary Care Companion For CNS... Jan 2020
Topics: Adult; Antidepressive Agents; Bupropion; Dysthymic Disorder; Ejaculation; Humans; Male
PubMed: 31917530
DOI: 10.4088/PCC.19l02453