CYP2B6 genotype alters abstinence rates in a bupropion smoking cessation trial.
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.
Lee
Anna M
AM
Centre for Addiction and Mental Health and the Department of Pharmacology, University of Toronto, 1 King's College Circle. Toronto, Ontario, Canada.
Jepson
Christopher
C
Hoffmann
Ewa
E
Epstein
Leonard
L
Hawk
Larry W
LW
Lerman
Caryn
C
Tyndale
Rachel F
RF
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D001521:Behavior Therapy; D016739:Behavior, Addictive / Q000188:drug therapy / Q000523:psychology; D016642:Bupropion / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D065637:Cytochrome P-450 CYP2A6; D065702:Cytochrome P-450 CYP2B6; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D010597:Pharmacogenetics; D010919:Placebos; D011110:Polymorphism, Genetic / Q000235:genetics; D012907:Smoking / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D016540:Smoking Cessation / Q000379:methods*; D014029:Tobacco Use Disorder / Q000188:drug therapy / Q000235:genetics / Q000523:psychology; D016896:Treatment Outcome
D010919:Placebos; D016642:Bupropion; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065637:Cytochrome P-450 CYP2A6; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating