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Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy

Molecular Psychiatry volume 11, pages 400–409 (2006)Cite this article

Abstract

We investigated the effect of slow metabolism of nicotine, predicted by CYP2A6 genotypes resulting in ⩽50% activity, on baseline smoking behaviours and treatment variables in an open-label nicotine replacement therapy (NRT) clinical trial. Caucasian smokers with CYP2A6 slow vs normal metabolism had lower metabolic activity, indicated by the 3-hydroxycotinine/cotinine ratio (0.23±0.17 vs 0.45±0.22, P<0.01, respectively). CYP2A6 slow metabolizers also smoked fewer cigarettes per day compared to normal metabolizers (20±7 vs 24±10, respectively, P<0.04). With nicotine patch use, slow metabolizers had higher nicotine plasma levels compared to normal metabolizers (22.8±4.6 vs 15.8±7.6 ng/ml, respectively, P=0.02) while using the same numbers of patches/week. With nicotine spray use, where like in smoking the nicotine intake can be easily adjusted to adapt to rates of metabolism, slow metabolizers achieved similar nicotine levels compared to normal metabolizers (5.8±4.1 vs 8.0±9.1 ng/ml, P=0.82), by using fewer doses of nicotine spray/day (4.8±3.6 vs 10.5±8.0, respectively, P<0.02). These findings indicate that CYP2A6 genotype influences smoking behaviour in a Caucasian treatment-seeking population and that CYP2A6 genotype affects plasma levels obtained from, and usage of, NRT.

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Acknowledgements

This work was supported by a CIHR Grant MOP 53248, the Centre for Addiction and Mental Health (RFT), a Transdisciplinary Tobacco Use Research Center Grant from the National Cancer Institute and the National Institute on Drug Abuse P5084718, the Abramson Cancer Center and Annenberg Public Policy Center (CL), PHS Grants DA02277, DA12393, CA078703, and the UCSF Comprehensive Cancer Center (NB), and a Public Health Services Research Grant M01-RR0040 from the National Institutes of Health. We would like to acknowledge the technical support of Ewa Hoffmann, Yushu Rao and Bo Xu. We also acknowledge the support of a CIHR-STPTR award (VM) and a Canada Research Chair in Pharmacogenetics (RFT). Nicotine nasal spray (Nicotrol®) was provided by Pharmacia, Helsingborg, Sweden.

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Authors and Affiliations

  1. Centre for Addiction and Mental Health and Department of Pharmacology, University of Toronto, Toronto, ON, Canada

    V Malaiyandi & R F Tyndale

  2. Department of Psychiatry and Abramson Cancer Center, Transdisciplinary Tobacco Use Research Center, University of Pennsylvania, Philadelphia, PA, USA

    C Lerman, C Jepson & F Patterson

  3. Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, University of California, San Francisco, CA, USA

    N L Benowitz

  4. Departments of Medicine, Psychiatry and Biopharmaceutical Sciences, University of California, San Francisco, CA, USA

    N L Benowitz

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  1. V Malaiyandi
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  3. N L Benowitz
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Correspondence to R F Tyndale.

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Malaiyandi, V., Lerman, C., Benowitz, N. et al. Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy. Mol Psychiatry 11, 400–409 (2006). https://doi.org/10.1038/sj.mp.4001794

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