The Nicotine Metabolite Ratio is Associated With Early Smoking Abstinence Even After Controlling for Factors That Influence the Nicotine Metabolite Ratio

Abstract

Introduction: The decrease in smoking rates in North America has plateaued, underscoring the need for new approaches to treat nicotine dependence. Inter-individual differences in smoking behavior result, in part, from variation in the rate of CYP2A6-mediated nicotine metabolism. A phenotypic measure of CYP2A6 activity is the nicotine metabolite ratio (NMR), the ratio of 3'hydroxycotinine/cotinine. The NMR is associated with smoking cessation. However, the NMR is also associated with genetic (eg, CYP2A6 genotype) and other (eg, sex and ethnicity) factors. Here we aimed to determine if previously identified non-CYP2A6 sources of variation in the NMR mitigated the association between the NMR and short-term abstinence.

Methods: The NMR was determined from blood samples collected at intake from daily smokers aged 18-65. Biochemically-verified point prevalence abstinence (exhaled carbon monoxide level ≤ 8 ppm) was measured at 1 week following the target quit date in participants from a smoking cessation clinical trial (NCT01314001). Analyses were restricted to N = 462 blacks and N = 693 whites in the intent-to-treat sample.

Results: Lower NMR (<0.31) was associated with a higher likelihood of 1-week abstinence (OR = 1.43; 95% CI = 1.12, 1.84). NMR was associated with abstinence even after controlling for treatment arm (nicotine patch or varenicline) and factors previously associated with NMR variation including sex, ethnicity, estrogen-containing hormonal therapy, body mass index, alcohol, and cigarette consumption.

Conclusions: NMR was associated with 1-week smoking abstinence; NMR may be a useful addition to medication screening approaches evaluating treatments for nicotine dependence.