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Association of nicotine metabolite ratio and CYP2A6 genotype with smoking cessation treatment in African-American light smokers.

ABSTRACT: Cytochrome P450 2A6 (CYP2A6) is the main nicotine (NIC)-metabolizing enzyme in humans. We investigated the relationships between CYP2A6 genotype, baseline plasma trans- 3'-hydroxycotinine/cotinine (3HC/COT) (a phenotypic marker of CYP2A6 activity), and smoking behavior in African-American light smokers. Cigarette consumption, age of initiation, and dependence scores did not differ among 3HC/COT quartiles or CYP2A6 genotype groups. Slow metabolizers (SMs; both genetic and phenotypic) had significantly higher plasma NIC levels, suggesting that cigarette consumption was not reduced to adjust for slower rates of NIC metabolism. Individuals in the slowest 3HC/COT quartile had higher quitting rates with both placebo and NIC gum treatments (odds ratio 1.85, 95% confidence interval (CI) 1.08-3.16, P = 0.03). Similarly, the slowest CYP2A6 genotype group had higher quitting rates, although this trend did not reach significance (odds ratio 1.61, 95% CI 0.95-2.72, P = 0.08). The determination of the 3HC/COT ratio, and possibly CYP2A6 genotype, may be useful in the future for personalizing the choice of smoking cessation treatment in African-American light smokers.

SUBMITTER: Ho MK

PROVIDER: S-EPMC3698861 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Association of nicotine metabolite ratio and CYP2A6 genotype with smoking cessation treatment in African-American light smokers.

Ho M K MK Mwenifumbo J C JC Al Koudsi N N Okuyemi K S KS Ahluwalia J S JS Benowitz N L NL Tyndale R F RF

Clinical pharmacology and therapeutics 20090311 6

Cytochrome P450 2A6 (CYP2A6) is the main nicotine (NIC)-metabolizing enzyme in humans. We investigated the relationships between CYP2A6 genotype, baseline plasma trans- 3'-hydroxycotinine/cotinine (3HC/COT) (a phenotypic marker of CYP2A6 activity), and smoking behavior in African-American light smokers. Cigarette consumption, age of initiation, and dependence scores did not differ among 3HC/COT quartiles or CYP2A6 genotype groups. Slow metabolizers (SMs; both genetic and phenotypic) had signific ...[more]

PMID: 19279561

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Project description:Previous research demonstrated the efficacy of sustained release bupropion (bupropion SR) for smoking cessation in whites as well as moderate to heavy (?10 cigarettes per day [CPD]) African American smokers. We evaluated whether bupropion SR was effective for smoking cessation among African American light smokers (?10 CPD).A randomized, double-blind placebo-controlled trial was conducted from December 27, 2007, to May 13, 2010. All participants were African American light smokers (?10 CPD), aged 18 years or older. Participants were randomly assigned to receive 300 mg bupropion SR (150 mg once daily for 3 days and then 150 mg twice daily) (n = 270 participants) or placebo (n = 270 participants) for 7 weeks, and up to six sessions of health education counseling. Serum cotinine was measured at baseline (week 0). The primary outcome was salivary cotinine-verified 7-day point prevalence smoking abstinence at week 26; a cut point of 15 ng/mL differentiated smokers from nonsmokers. Salivary cotinine-verified smoking abstinence at end of medication treatment at week 7 was also examined. Odds ratios (OR) for smoking abstinence and 95% confidence intervals (CIs) were calculated using logistic regression models. All statistical tests were two-sided.Participants at baseline visit (week 0) smoked an average of 8.0 CPD and had a mean serum cotinine level of 275.8 ng/mL (SD = 155.8 ng/mL); most used menthol cigarettes (83.7%) and smoked within 30 minutes of waking (72.2%). After imputing those lost to follow-up as smokers, no statistically significant difference in long-term smoking abstinence rates at week 26 was observed between bupropion SR and placebo groups (13.3% vs 10.0%, OR = 1.39, 95% CI = 0.82 to 2.35, P = .23). Cotinine-verified smoking abstinence rate at end of medication week 7 was higher in the bupropion SR vs placebo group (23.7% vs 9.6%, OR = 2.92, 95% CI = 1.78 to 4.77, P < .001).Bupropion SR was effective in promoting smoking cessation during the medication phase of treatment but showed no effect on long-term smoking cessation among African American light smokers. More research is needed to identify strategies for sustaining abstinence among African American light smokers.

Project description:Background and aimsIn smoking treatment trials comparing varenicline with transdermal nicotine replacement therapy (NRT), stratified by nicotine metabolite (3-hydroxycotinine/cotinine) ratio (NMR), the relative benefit of varenicline is greater among normal rather than slow metabolizers. This study tested if the relative effectiveness of varenicline and NRT is associated with NMR status in a natural treatment setting. A secondary aim was to test if this relationship is moderated by behavioural support.DesignProspective observational multi-centre study with 4-week and 52-week follow-up.SettingNine English Stop Smoking Services (SSS).ParticipantsData came from 1556 smokers (aged ≥ 16 years) attending SSS between March 2012 and March 2013.InterventionsParticipants received pharmacotherapy together with behavioural support.MeasurementsThe primary outcome was carbon monoxide-verified continuous abstinence at both follow-up times. Main explanatory variables were (1) NMR status [slow (NMR < 0.31, n = 451) versus normal (NMR ≥ 0.31, n = 1105) metabolizers]; (2) pharmacotherapy (varenicline versus NRT) and (3) behavioural support (individual versus group-based treatment). Analyses adjusted for baseline socio-demographic, SSS, mental/physical health and smoking characteristics.FindingsOf participants, 44.2% [95% confidence interval (CI) = 41.7-46.6%] and 8.0% (95% CI = 6.8-9.5%) were continuously abstinent at 4 and 52 weeks. Varenicline was more effective than NRT at 4 weeks (P < 0.001) but only marginally so at 52 weeks (P = 0.061). There was no or inclusive evidence that NMR status moderated relative efficacy of varenicline and NRT at 4- [P = 0.60, Bayes factor (BF) = 0.25] or 52-week follow-ups (P = 0.74, BF = 0.73). However, this relationship was moderated by behavioural support (p = 0.012): the relative benefit of varenicline over NRT at 52-week follow-up was greater in slow, not normal, metabolizers receiving group rather than individual support (P = 0.012).ConclusionsIn a real-world setting, the nicotine metabolite ratio status of treatment-seeking smokers does not appear to contribute substantially to the differential effectiveness of varenicline and nicotine replacement therapy in Stop Smoking Services, when both pharmacotherapy and behavioural support are self-selected.

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Dataset Information

Association of nicotine metabolite ratio and CYP2A6 genotype with smoking cessation treatment in African-American light smokers.

Publications

Association of nicotine metabolite ratio and CYP2A6 genotype with smoking cessation treatment in African-American light smokers.

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