title: Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy.
abstract: We investigated the effect of slow metabolism of nicotine, predicted by CYP2A6 genotypes resulting in less than or equal to 50% activity, on baseline smoking behaviours and treatment variables in an open-label nicotine replacement therapy (NRT) clinical trial. Caucasian smokers with CYP2A6 slow vs normal metabolism had lower metabolic activity, indicated by the 3-hydroxycotinine/cotinine ratio (0.23+/-0.17 vs 0.45+/-0.22, P<0.01, respectively). CYP2A6 slow metabolizers also smoked fewer cigarettes per day compared to normal metabolizers (20+/-7 vs 24+/-10, respectively, P<0.04). With nicotine patch use, slow metabolizers had higher nicotine plasma levels compared to normal metabolizers (22.8+/-4.6 vs 15.8+/-7.6 ng/ml, respectively, P=0.02) while using the same numbers of patches/week. With nicotine spray use, where like in smoking the nicotine intake can be easily adjusted to adapt to rates of metabolism, slow metabolizers achieved similar nicotine levels compared to normal metabolizers (5.8+/-4.1 vs 8.0+/-9.1 ng/ml, P=0.82), by using fewer doses of nicotine spray/day (4.8+/-3.6 vs 10.5+/-8.0, respectively, P<0.02). These findings indicate that CYP2A6 genotype influences smoking behaviour in a Caucasian treatment-seeking population and that CYP2A6 genotype affects plasma levels obtained from, and usage of, NRT.
authors.affiliation: Centre for Addiction and Mental Health and Department of Pharmacology, University of Toronto, Toronto, ON, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Malaiyandi
authors.forename: C
authors.initials: C
authors.lastname: Lerman
authors.forename: N L
authors.initials: NL
authors.lastname: Benowitz
authors.forename: C
authors.initials: C
authors.lastname: Jepson
authors.forename: F
authors.initials: F
authors.lastname: Patterson
authors.forename: R F
authors.initials: RF
authors.lastname: Tyndale
mesh_terms: D000279:Administration, Cutaneous; D000280:Administration, Inhalation; D000328:Adult; D000704:Analysis of Variance; D001189:Aryl Hydrocarbon Hydroxylases / Q000187:drug effects / Q000235:genetics*; D016009:Chi-Square Distribution; D065637:Cytochrome P-450 CYP2A6; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000187:drug effects / Q000235:genetics*; D009538:Nicotine / Q000008:administration & dosage / Q000097:blood*; D012016:Reference Values; D012907:Smoking / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D016540:Smoking Cessation; D018709:Statistics, Nonparametric; D014029:Tobacco Use Disorder / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome; D044465:White People / Q000235:genetics
chemical_list: D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6