CYP2B6 Genotype Alters Abstinence Rates in a Bupropion Smoking Cessation Trial

Lee, Anna M.; Jepson, Christopher; Hoffmann, Ewa; Epstein, Leonard; Hawk, Larry W.; Lerman, Caryn; Tyndale, Rachel F.

doi:10.1016/j.biopsych.2006.10.005

« Previous Next »Biological Psychiatry
Volume 62, Issue 6 , Pages 635-641, 15 September 2007

CYP2B6 Genotype Alters Abstinence Rates in a Bupropion Smoking Cessation Trial

Anna M. Lee
- Centre for Addiction and Mental Health and the Department of Pharmacology, University of Toronto, Ontario, Canada
Christopher Jepson
- Department of Psychiatry, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania
Ewa Hoffmann
- Centre for Addiction and Mental Health and the Department of Pharmacology, University of Toronto, Ontario, Canada
Leonard Epstein
- Department of Pediatrics, School of Medicine and Biomedical Sciences, The University at Buffalo, State University of New York, Buffalo, New York
Larry W. Hawk
- Department of Psychology, The University at Buffalo, State University of New York, Buffalo, New York.
Caryn Lerman
- Department of Psychiatry, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania
Rachel F. Tyndale
- Centre for Addiction and Mental Health and the Department of Pharmacology, University of Toronto, Ontario, Canada
- 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

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.

Key Words: Bupropion, CYP2A6, CYP2B6, genetic, nicotine, pharmacogenetic, smoking