CYP2B6 Genotype Alters Abstinence Rates in a Bupropion Smoking Cessation Trial
Received 2 July 2006; received in revised form 4 October 2006; accepted 5 October 2006. published online 17 January 2007.
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.
aCentre for Addiction and Mental Health and the Department of Pharmacology, University of Toronto, Ontario, Canada
bDepartment of Psychiatry, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania
cDepartment of Pediatrics, School of Medicine and Biomedical Sciences, The University at Buffalo, State University of New York, Buffalo, New York
dDepartment of Psychology, The University at Buffalo, State University of New York, Buffalo, New York.
Address reprint requests to Rachel F. Tyndale, M.Sc., Ph.D., University of Toronto, Department of Pharmacology, 1 King’s College Circle, Room 4326, Toronto, Ontario M5S 1A8, Canada
ABSTRACT