Background: CYP2B6 is the primary enzyme involved in bupropion (Zyban; GlaxoSmithKline, Research Triangle Park, North Carolina) metabolism. Genetic polymorphisms in CYP2B6, such as CYP2B6*6, can alter bupropion metabolism and may affect bupropion treatment outcome. Methods: Subjects participated in a smoking cessation clinical trial of bupropion versus placebo. The main outcome was a 7-day point prevalence abstinence rate measured 10 weeks after the start of treatment (i.e., end of treatment) and at the 6-month follow-up; secondary outcomes were severity of adverse effects, withdrawal, and urge to smoke. Subjects were haplotyped for the CYP2B6*6 variants. Results: Among smokers in the CYP2B6*6 group (CYP2B6*1/*6 or CYP2B6*6/*6 genotype, n = 147, 45% of the population), bupropion produced significantly higher abstinence rates than placebo at the end of treatment (32.5% vs. 14.3%, p = .01) and at the 6-month follow-up (31.2% vs. 12.9%, p = .008). In contrast, bupropion was no more effective than placebo for smokers in the CYP2B6*1 group (CYP2B6*1/*1, n = 179) at the end of treatment (31.0% vs. 31.6%, p = .93) or at the 6-month follow-up (22.0% vs. 21.5%, p = .94). There was a significant genotype by treatment interaction at the end of treatment (odds ratio [OR] = 2.97, confidence interval [CI] = 1.05-8.40, p = .04), which was similar at 6-month follow-up (OR = 2.98, CI = .98-9.06, p = .05). Conclusions: These data suggest that smokers with the CYP2B6*6 genotype have a higher liability to relapse on placebo and that they may be good candidates for bupropion treatment for smoking cessation.
Bibliographical noteFunding Information:
This work was supported by a Canadian Tobacco Control Research Initiative student grant 16803 (AML), Canadian Institute of Health Research (CIHR) Tobacco Use in Special Populations Fellowship (AML), grants from the National Cancer Institute and National Institutes on Drug Abuse, P5084718, RO1 CA63562 (CL) and DA020830 (RFT, CL), CIHR grant MOP53248 (RFT), and a Canada Research Chair in Pharmacogenetics (RFT). Study medication was provided at no cost by GlaxoSmithKline.