Managing smoking cessation

Reid, Robert D.; Pritchard, Gillian; Walker, Kathryn; Aitken, Debbie; Mullen, Kerri-Anne; Pipe, Andrew

doi:10.1503/cmaj.151510

Cited by 41 publications

(37 citation statements)

References 67 publications

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“…Bupropion is a mainstay in treating major depressive disorder, alone or in combination. 1 Bupropion is also used for smoking cessation, 2 and to treat obesity, 3 attention deficit hyperactivity disorder, 4 seasonal affective disorder, 5 cocaine or amphetamine abuse, 6,7 and chronic pain. 8 Bupropion is used clinically as a racemate.…”

mentioning

confidence: 99%

Stereoselective Steady‐State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults

Kharasch

Neiner

Kraus

et al. 2020

Clin Pharma and Therapeutics

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The antidepressant bupropion is stereoselectively metabolized and metabolite enantiomers have differential pharmacologic effects, but steady-state enantiomeric disposition is unknown. Controversy persists about bupropion XL 300 mg generic equivalence to brand product, and whether generics might have different stereoselective disposition leading to enantiomeric non-bioequivalence and, thus, clinical nonequivalence. This preplanned follow-on analysis of a prospective, randomized, double-blinded, crossover study of brand and 3 generic bupropion XL 300 mg products measured steady-state enantiomeric plasma and urine parent bupropion and primary and secondary metabolite concentrations and evaluated bioequivalence and pharmacokinetics. Steady-state plasma and urine bupropion disposition was markedly stereoselective, with up to 40-fold differences in plasma concentrations of the active metabolite S,S-hydroxybupropion vs. R,R,-hydroxybupropion. Urine metabolite glucuronides were prominent, but glucuronidation was metabolite-specific and enantioselective. There were no differences between any generic and brand, or between generics, in plasma enantiomer concentrations of bupropion or the major metabolites. All generic products satisfied formal bioequivalence criteria (peak plasma concentration (C max) and area under the plasma concentration-time curve over 24 hours (AUC 0-24)) using enantiomers for bupropion as well as for metabolites, and generics were comparable to each other, and were considered bioequivalent, based on enantiomeric analysis. Enantiomeric bioequivalence explains the previously observed therapeutic equivalence of bupropion generics and brand in treating major depression. These results have important implications for understanding the clinical therapeutic effects of bupropion based on complex and stereoselective metabolism.

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mentioning

confidence: 99%

Stereoselective Steady‐State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults

Kharasch

Neiner

Kraus

et al. 2020

Clin Pharma and Therapeutics

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“…It is also a first‐line switch agent for patients intolerant to or nonresponsive to selective serotonin reuptake inhibitors. Bupropion is also used for seasonal affective disorder, smoking cessation, obesity, and attention deficit hyperactivity disorder in adults and children . Bupropion undergoes extensive metabolism, with less than 1% recovered intact in urine, to the three primary metabolites hydroxybupropion (via t ‐butylhydroxylation), and the isomers threohydrobupropion and erythrohydrobupropion (via keto reduction).…”

mentioning

confidence: 99%

Common Polymorphisms of CYP2B6 Influence Stereoselective Bupropion Disposition

Kharasch

Crafford

2018

Clin Pharma and Therapeutics

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Bupropion hydroxylation is a bioactivation and metabolic pathway, and the standard clinical CYP2B6 probe. This investigation determined the influence of CYP2B6 allelic variants on clinical concentrations and metabolism of bupropion enantiomers. Secondary objectives evaluated the influence of CYP2C19 and P450 oxidoreductase variants. Healthy volunteers in specific cohorts (CYP2B6*1/*1, CYP2B6*1/*6, CYP2B6*6/*6, and also CYP2B6*4 carriers) received single-dose oral bupropion. Plasma and urine bupropion and hydroxybupropion was quantified. Subjects were also genotyped for CYP2C19 and P450 oxidoreductase variants. Hydroxylation of both bupropion enantiomers, assessed by plasma hydroxybupropion/bupropion AUC ratios and urine hydroxybupropion formation clearances, was lower in CYP2B6*6/*6 but not CYP2B6*1/*6 compared with CYP2B6*1/*1 genotypes, and numerically greater in CYP2B6*4 carriers. CYP2C19 and P450 oxidoreductase variants did not influence bupropion enantiomers hydroxylation or plasma concentrations. The results show that clinical hydroxylation of both bupropion enantiomers was equivalently influenced by CYP2B6 allelic variation. CYP2B6 polymorphisms affect S-bupropion bioactivation, which may affect therapeutic outcomes.

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“…Only 12 (16.7%) participants had ever tried oral therapy to quit smoking and only 4 (5.6%) had ever received counselling to quit smoking. In the general population, bupropion nearly doubles the odds of abstinence at 12 months compared to placebo (OR 1.85, 95% CI 1.63-2.10) and varenicline nearly triples the odds (OR 2.89, 95% CI 2.40-3.48), whereby the abstinence rate of control participants is about 10% [33]. Few Randomized Controlled Trials (RCTs) have been conducted in PLHIV, but these treatments appear to be efficacious and well-tolerated [29].…”

Section: Discussionmentioning

confidence: 99%

“…Smoking cessation counselling is another effective intervention used in the general population, with increased relative quit rates of 1.39 (95%CI: 1.24 to 1.57) and 1.98 (95%CI: 1.60 to 2.46) for individual and group counselling, respectively [33]. Studies of smoking cessation counseling in PLHIV have been hindered by methodological issues such as small sample sizes or lack of randomization [29].…”

Section: Discussionmentioning

confidence: 99%

Use of Smoking Cessation Aids in a Convenience Sample of PLHIV in a Canadian Tertiary Care Clinic

Linthwaite¹,

Cox²,

Klein³

et al. 2019

TOAIDJ

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Background: Tobacco smoking is among the most significant predictors of cardiovascular disease and lung cancer in People Living with HIV (PLHIV). Smoking rates in this population are high, necessitating more effective smoking cessation strategies. We conducted a descriptive analysis of tobacco-related clinical and sociodemographic characteristics of smokers at a tertiary care HIV clinic in Montreal and an exploratory analysis of smoking cessation methods in order to identify potential areas of improvement in the clinic’s approach to smoking cessation. Methods: A convenience sample of patients completed a 10-minute questionnaire on tobacco-related behaviours and outcomes. Use of smoking cessation methods was compared using McNemar’s exact test with a Bonferroni correction for multiple testing (p<0.01 considered significant). Results: Seventy-two PLHIV participated. Two-thirds of our total participants were interested in quitting within six months, but the use of effective cessation strategies was low, particularly for counseling and oral therapy. Overall, oral therapy (e.g. varenicline) (16.7%) and counseling for cessation (5.6%) were used less than nicotine patches (50.0%) or ‘other’ methods (50.0%), which included abstinence and nicotine gum (p<0.001). Conclusion: Despite a small and potentially unrepresentative sample of HIV positive tobacco smokers at our clinic, this study could help guide further research aiming to determine and address barriers to smoking cessation and access to effective smoking cessation aids in PLHIV. Future studies might consider factors that affect motivation to quit, such as co-morbid mental health and substance use disorders, or the attitudes of HIV healthcare providers.

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Managing smoking cessation

Cited by 41 publications

References 67 publications

Stereoselective Steady‐State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults

Stereoselective Steady‐State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults

Common Polymorphisms of CYP2B6 Influence Stereoselective Bupropion Disposition

Use of Smoking Cessation Aids in a Convenience Sample of PLHIV in a Canadian Tertiary Care Clinic

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