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Review
. 2016 Sep;11(3):471-83.
doi: 10.1007/s11481-016-9656-y. Epub 2016 Feb 12.

Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio

Cheyenne E Allenby  1 , Kelly A Boylan  1 , Caryn Lerman  1 , Mary Falcone  2
Affiliations
Review

Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio

Cheyenne E Allenby et al. J Neuroimmune Pharmacol. 2016 Sep.

Abstract

Quitting smoking significantly reduces the risk of tobacco-related morbidity and mortality, yet there is a high rate of relapse amongst smokers who try to quit. Phenotypic biomarkers have the potential to improve smoking cessation outcomes by identifying the best available treatment for an individual smoker. In this review, we introduce the nicotine metabolite ratio (NMR) as a reliable and stable phenotypic measure of nicotine metabolism that can guide smoking cessation treatment among smokers who wish to quit. We address how the NMR accounts for sources of variation in nicotine metabolism including genotype and other biological and environmental factors such as estrogen levels, alcohol use, body mass index, or menthol exposure. Then, we highlight clinical trials that validate the NMR as a biomarker to predict therapeutic response to different pharmacotherapies for smoking cessation. Current evidence supports the use of nicotine replacement therapy for slow metabolizers, and non-nicotine treatments such as varenicline for normal metabolizers. Finally, we discuss future research directions to elucidate mechanisms underlying NMR associations with treatment response, and facilitate the implementation of the NMR as biomarker in clinical practice to guide smoking cessation.

Keywords: Nicotine; Nicotine addiction; Nicotine metabolite ratio; Smoking cessation.

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Conflict of interest statement

Conflicts of Interest

Dr. Lerman received donated drug and placebo supplies from Pfizer for conducting a randomized clinical trial. The other authors report no conflicts of interest.

Figures

Figure 1
Figure 1. Quit Rates by Treatment Arm and NMR Group
The NMR predicts treatment outcomes on nicotine replacement therapy and varenicline Smoking cessation rates by NMR and treatment group. Varenicline treatment significantly improved quit rates compared to the nicotine patch among normal metabolizers; however, among slow metabolizers, varenicline was no better than the nicotine patch at promoting cessation. Adapted from Lerman et al. 2015.
Figure 2
Figure 2. Incorporating the NMR to aid in smoking cessation treatment selection
A proposed model for incorporating the NMR into smoking cessation treatment decision-making.
See this image and copyright information in PMC

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