These findings extend the existing research on CYP2A6 and the Nicotine Metabolite Ratio (NMR). The NMR is a direct biomarker of nicotine metabolism that reflects both genetic and environmental influences on nicotine metabolism and clearance (21). In general, faster nicotine metabolism as estimated by NMR has predicted reduced smoking cessation success when individuals were given the nicotine patch, gum, or placebo, but not when given nicotine nasal spray or bupropion (14, 22). Using estimated nicotine metabolism based on CYP2A6 genotypes, we provide additional evidence regarding the effects of specific pharmacotherapies from a large scale trial. We confirm that faster nicotine metabolism is associated with greater relapse likelihood in the placebo condition, and we also find that nicotine metabolism is unrelated to response to bupropion treatment. The latter observation is consistent with existing evidence (13) and the fact that bupropion is primarily metabolized by the CYP2B6 enzyme (23, 24). Instead of using NMR, this study presents the first genotype by NRT interaction with a proper placebo-control arm. Our findings differ from earlier reports primarily because we found that nicotine metabolism did
