Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy

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Abstract
We investigated the effect of slow metabolism of nicotine, predicted by CYP2A6 genotypes resulting in 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, PPP=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, PCYP2A6 genotype influences smoking behaviour in a Caucasian treatment-seeking population and that CYP2A6 genotype affects plasma levels obtained from, and usage of, NRT.