A recent pharmacogenetic trial of NRT with over 300 participants examined whether CYP2A6 genotype (or phenotype based on 3-HC/cotinine ratio) predicts treatment outcome (Malaiyandi et al., 2006b). Among participants in this open-label trial of nicotine patch versus nicotine nasal spray (Malaiyandi et al., 2006b), slower metabolizers (i.e., those with one null allele or two reduced activity alleles) had significantly higher treatment levels of plasma nicotine from the patch than normal metabolizers, with equivalent rates of compliance. In contrast, among those randomized to receive nicotine nasal spray, the slow metabolizers self-administered fewer doses of the spray, as compared to the normal metabolizers, resulting in equivalent levels of plasma nicotine (Malaiyandi et al., 2006b). A second study reported that smokers with the reduced activity CYP2A6 variants were more sensitive to the effects of the patch, causing them to relapse after a quit attempt (Ozaki et al., 2006); however, the sample size (n = 41) was too small to be conclusive.
