Genetic variation in nicotine metabolism predicts the efficacy of extended-duration transdermal nicotine therapy

Abstract

In a placebo-controlled trial, we examined the efficacy of a 6-month ("extended") transdermal nicotine therapy vs. the 8-week ("standard") therapy in 471 Caucasian smokers with either normal or reduced rates of nicotine metabolism as determined at pretreatment. Extended therapy was superior to standard therapy in genotypic or phenotypic reduced metabolizers (RMs) of nicotine but not in normal metabolizers (NMs). RMs of nicotine are candidates for extended transdermal nicotine therapy, whereas an alternative therapeutic approach may be needed for those with normal rates of nicotine metabolism.

Figure 1

The impact of reduced nicotine metabolism on the efficacy of extended vs. standard duration transdermal nicotine therapy. (a) Differences between CYP2A6 genotype groups as regards response to extended vs. standard therapy (RM-G = reduced metabolism genotype; NM-G = normal metabolism genotype). (b) Differences between baseline nicotine metabolite ratio (3HC/cotinine) phenotype groups with respect to response to extended vs. standard therapy (RM-P = reduced metabolism phenotype; NM-P = normal metabolism phenotype). 3HC, 3′-hydroxycotinine.

Figure 2

Flowchart of study participation. CO, carbon monoxide; NMR, nicotine metabolite ratio.