Nicotine metabolic rate predicts successful smoking cessation with transdermal nicotine: a validation study

Abstract

Transdermal nicotine is widely used for smoking cessation, but only approximately 20% of smokers quit successfully with this medication. Interindividual variability in nicotine metabolism rate may influence treatment response. This study sought to validate, and extend in a larger sample, our previous finding that the ratio of plasma nicotine metabolites 3'-hydroxycotinine (3-HC)/cotinine, a measure of nicotine metabolism rate, predicts response to nicotine patch. A sample of 568 smokers was enrolled in a study that provided counseling and 8-weeks of 21 mg nicotine patch. Pretreatment 3-HC/cotinine ratio was examined as a predictor of 7-day point prevalence abstinence, verified with breath carbon monoxide (CO), 8 weeks after the quit date. Controlling for sex, race, age, and nicotine dependence, smokers in the upper 3 quartiles of 3-HC/cotinine ratio (faster metabolizers) were approximately 50% less likely to be abstinent vs. smokers in the first quartile (slow metabolizers; 28% vs. 42%; OR=.54 [95% CI:.36-.82], p=.003). Among abstainers, plasma nicotine levels (assessed 1 week after treatment began) decreased linearly across the 3-HC/cotinine ratio (beta=-3.38, t[355]=-3.09, p<.05). These data support the value of the 3-HC/cotinine ratio as a biomarker to predict success with transdermal nicotine for smoking cessation.

Conflict of interest statement

Conflicts of Interest: Dr. Lerman has served as a consultant to GlaxoSmithKline, the company that manufactures the nicotine patch used in this study. However, GSK did not provide medication or financial support for this study. Dr. Tyndale is a shareholder and CSO for Nicogen, a company focused on novel smoking cessation approaches. No funding was provided from Nicogen for this study. Dr Benowitz has been a paid consultant to several pharmaceutical companies that market and/or are developing medications for smoking cessation. He has also served as a paid expert witness in litigation against tobacco companies.

Figures

Figure 1

Participant Flow. Note. * A list of the reasons for participant ineligibility can be provided by the authors upon request; ** included in intent-to-treat analysis.

Figure 2

Study Design. Note. R = Recruitment; BSL = Baseline; TN = transdermal nicotine; W = Week; * indicates CO-confirmed abstainers only; ** indicates inclusion of 63 participants who withdrew from the study and 136 participants who did not provide data at Week 8.

Figure 3

Week 1 Plasma Nicotine Values Across 3-HC/Cotinine Ratio Quartiles (Abstainers Only, n = 386). Note. Log 3-HC/cotinine ratio is significantly related to nicotine plasma levels one week after treatment began among confirmed abstainers (β = −3.48, t[385] = −3.33, p < .05).

Figure 4

Week 8 Quit Rates (7-day Point Prevalence, CO-confirmed) Across 3-HC/Cotinine Ratio Quartiles (n = 568). Note. 3-HC/cotinine ratio is significantly related to 7-day point prevalence quit rates, CO-confirmed (OR = .66, 95% CI: .48–.91, p < .05). N’s for each quartile are 142.