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CYP2B6 and bupropion's smoking-cessation pharmacology: the role of hydroxybupropion.

ABSTRACT: Bupropion is indicated to promote smoking cessation. Animal studies suggest that the pharmacologic activity of bupropion can be mediated by its major metabolite, hydroxybupropion. We measured plasma bupropion and its metabolite levels in a double-blind, placebo controlled, randomized smoking-cessation trial. Among the treatment-adherent individuals, higher hydroxybupropion concentrations (per ?g/ml) resulted in better smoking-cessation outcomes (week 3, 7, and 26 odds ratio (OR) = 2.82, 2.96, and 2.37, respectively, P = 0.005-0.040); this was not observed with bupropion levels (OR = 1.00-1.03, P = 0.59-0.90). Genetic variation in CYP2B6, the enzyme that metabolizes bupropion to hydroxybupropion, was identified as a significant source of variability in hydroxybupropion formation. Our data indicate that hydroxybupropion contributes to the pharmacologic effects of bupropion for smoking cessation, and that variability in response to bupropion treatment is related to variability in CYP2B6-mediated hydroxybupropion formation. These findings suggest that dosing of bupropion to achieve a hydroxybupropion level of 0.7 ?g/ml or increasing bupropion dose for CYP2B6 slow metabolizers could improve bupropion's cessation outcomes.

SUBMITTER: Zhu AZ

PROVIDER: S-EPMC3729209 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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CYP2B6 and bupropion's smoking-cessation pharmacology: the role of hydroxybupropion.

Zhu A Z X AZ Cox L S LS Nollen N N Faseru B B Okuyemi K S KS Ahluwalia J S JS Benowitz N L NL Tyndale R F RF

Clinical pharmacology and therapeutics 20121114 6

Bupropion is indicated to promote smoking cessation. Animal studies suggest that the pharmacologic activity of bupropion can be mediated by its major metabolite, hydroxybupropion. We measured plasma bupropion and its metabolite levels in a double-blind, placebo controlled, randomized smoking-cessation trial. Among the treatment-adherent individuals, higher hydroxybupropion concentrations (per μg/ml) resulted in better smoking-cessation outcomes (week 3, 7, and 26 odds ratio (OR) = 2.82, 2.96, an ...[more]

PMID: 23149928

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Project description:IntroductionSmoking denormalization has been paralleled by reduced smoking prevalence, but smoking rates among socioeconomically disadvantaged populations remain high. The social unacceptability of smoking has also led to increased perceptions of smoking-related stigma. By examining how smoking stigma influences cessation intervention effectiveness, we can better tailor interventions to socioeconomically disadvantaged smokers.Aims and methodsData are from a randomized controlled trial evaluating the effectiveness of a proactive cessation intervention on abstinence. Current smokers enrolled in Minnesota Health Care Programs were randomized to proactive outreach (n = 1200) or usual care (n = 1206). The intervention included mailings, telephone outreach, counseling, and access to free cessation treatments. Using baseline measurements, groups with lower (n = 1227) and higher (n = 1093) perceived stigma were formed. Intervention, stigma, and their interaction term were added to a logistic regression modeling abstinence at 12 months.ResultsLower perceived smoking-related stigma was associated with less support for quitting, lower rates of physician quitting advice, and less motivation for quitting. A logistic regression modeling abstinence found a significant intervention × stigma interaction. The proactive intervention was more effective among smokers with lower perceived smoking-related stigma (odds ratio 1.94, 95% confidence interval, 1.29 to 2.92) than those with higher perceived smoking-related stigma (odds ratio 1.04, 95% confidence interval, 0.70 to 1.55).DiscussionSmokers with lower perceived smoking-related stigma had social environments that were conducive to smoking, received less physician advice to quit, and were less motivated to quit than higher stigma smokers. Despite these barriers, the intervention was more effective for lower stigma smokers, suggesting that proactive outreach is an efficient treatment for these hard-to-reach smokers.ImplicationsSmoking denormalization has led to increased perceptions of smoking-related stigma among many smokers; however, little is known about how this stigma influences the cessation process. In the present study, smokers with lower levels of perceived smoking-related stigma lived in social environments that were more conducive to smoking and were less motivated to quit than higher stigma smokers. Despite these barriers, our proactive outreach cessation intervention was more effective for lower stigma smokers, suggesting that interventions which utilize proactive outreach to stimulate interest in quitting and offer facilitated access to free cessation treatments are an effective treatment approach for these hard-to-reach smokers. These strategies may be particularly effective for motivating smokers enrolled in government-subsidized health insurance programs to take advantage of cessation resources.

Project description:People who smoke make up a significant number of those admitted to hospital (NICE 2014). Being admitted to hospital can present a unique opportunity to attempt to stop smoking. Many smokers find quitting very difficult (Rigotti et al 2007), in large part due to them living and working in environments that contain many cues and triggers associated with nicotine consumption and smoking behaviours. Hospitals generally do not contain such environmental prompts to smoke. In the community, smokers have access to numerous types of support including GP's, pharmacies and Stop Smoking Services (SSS). Once admitted to hospital access to such support is significantly diminished. Given that many patients may be highly motivated to attempt to stop smoking due to heightened concerns about their health and being in an environment not associated with their smoking habits, it seems prudent to ensure there is access to all the levels of smoking cessation support available outside of the hospital. Not providing such support neglects implementing an evidence based, cost-effective health intervention in a major health setting (NICE 2014). A SSS pathway was designed that enabled existing hospital healthcare staff to be trained to identify patients that smoke, ask if the patient is considering quitting or abstaining whilst in hospital. If motivated to quit or abstain, to complete an assessment. This being based around dependence to nicotine and motivation to quit. Access to all available stop smoking medications should be included. Medication should only be provided alongside some level of motivational support up to discharge. Training core staff was felt to be the best option. They are available outside of office hours and access hospital systems such as pharmacy more readily than satellite staff. On discharge the patient is 'handed over' to SSS for continued contact and support once at home. Over 200 staff are trained to complete the assessment and support inpatients to stop or abstain. Approximately 30-35 referrals are made to the local SSS each month, the quit rate at 4 weeks averaging around 40-45%. Most referrals are seen from cardiology and respiratory. All hospital departments should identify staff to be trained to offer cessation support to their patients .

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CYP2B6 and bupropion's smoking-cessation pharmacology: the role of hydroxybupropion.

Publications

CYP2B6 and bupropion's smoking-cessation pharmacology: the role of hydroxybupropion.

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