The small number of smokers with reduced or null activity alleles in the Malaiyandi et al. (2006b) trial complicated the analysis of smoking cessation rates; therefore, this was examined by using the phenotypic marker of CYP2A6 activity (3-HC/cotinine ratio) (Lerman et al., 2006). As noted above, higher scores for the 3-HC/cotinine ratio reflect increased CYP2A6 activity (i.e., faster metabolism), while lower scores reflect decreased CYP2A6 activity (i.e., slower metabolism). Among individuals in the nicotine-patch condition (n = 193), there was a significant dose-response effect of nicotine metabolism rate (characterized by quartiles) on quitting at the end of 8 weeks treatment (from 46 to 27%) and at 6-month follow-up (from 30 to 11%). In fact, there was a 30% drop in the odds of remaining abstinent with each increasing quartile of the metabolite ratio (i.e., as nicotine metabolism increased, abstinence rate decreased) (Lerman et al., 2006). No such relationship was observed among smokers who received nicotine nasal spray (n = 201), presumably because they titrated their dose of treatment based on phenotype/genotype (Malaiyandi et al., 2006b). CYP2B6 genotype was unrelated to abstinence success in either the nicotine-patch or the nicotine-spray conditions in this trial (Lee et al., 2007b).
