CYP2A6 polymorphisms have also been shown to influence the pharmacokinetics of nicotine. This was clearly demonstrated in a study using intravenous infusion of D2-nicotine in carriers of the CYP2A6 *4, *2, *9, and *12 alleles [15]. However, the portion of variability in nicotine clearance explained by these alleles and a duplication allele associated with faster metabolism, was only 10% [20]. In addition, significant variation in nicotine clearance and in the trans 3′-hydroxycotinine to cotinine ratio exists in individuals identified as wild type [13, 15]. Taken together these data suggest that other as yet uncharacterized polymorphisms in CYP2A6 or other genes may contribute to nicotine metabolism and clearance. To accurately access the role of individual polymorphisms in nicotine metabolism it would be useful to develop a predictive model to transform genotype into a quantitative measure of relative enzyme activity.
