The role of CYP2A6 activity, based on the pretreatment nicotine-metabolite ratio (3-HC/cotinine), has also been examined in this bupropion pharmacogenetic cessation trial (Patterson et al., 2008). In the placebo condition (i.e., counseling alone), there was a dose-response effect of nicotine metabolism; end-of-treatment quit rates across the quartiles were (from slowest to fastest metabolism): 32, 25, 20, and 10%. This further substantiates the role of variation in CYP2A6-mediated nicotine metabolism in altering smoking behaviors, in this case quitting smoking. Bupropion improved quit rates among fastest metabolizers (4th quartile) from 10 to 34% at the end of treatment (Patterson et al., 2008). The slowest metabolizers had equivalent quit rates of 32% on bupropion and placebo. These data, together with the NRT study described above (Lerman et al., 2006), suggest that CYP2A6 slow metabolizers might benefit from a nicotine patch or counseling alone, while faster metabolizers may be excellent candidates for bupropion or another non-nicotine medication.
