Journal Article

Within-Subject Variation of the Salivary 3HC/COT Ratio in Regular Daily Smokers: Prospects for Estimating CYP2A6 Enzyme Activity in Large-Scale Surveys of Nicotine Metabolic Rate

Rod A. Lea, Stuart Dickson and Neal L. Benowitz

in Journal of Analytical Toxicology

Volume 30, issue 6, pages 386-389
Published in print July 2006 | ISSN: 0146-4760
Published online July 2006 | e-ISSN: 1945-2403 | DOI: http://dx.doi.org/10.1093/jat/30.6.386
Within-Subject Variation of the Salivary 3HC/COT Ratio in Regular Daily Smokers: Prospects for Estimating CYP2A6 Enzyme Activity in Large-Scale Surveys of Nicotine Metabolic Rate

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Nicotine is the major addictive compound in tobacco and is responsible for tobacco dependence. It is primarily metabolized to cotinine (COT) and trans-3′-hydroxycotinine (3HC) by the liver enzyme cytochrome P-450 2A6 (CYP2A6). The 3HC/COT ratio measured in the saliva of smokers is highly correlated with the intrinsic hepatic clearance of nicotine and, therefore, may be a useful non-invasive marker of CYP2A6 activity and metabolic rate of nicotine. This study assessed within-subject variation in salivary 3HC/COT ratios in six regular daily smokers. Our data provide evidence that 1, variation in the 3HC/COT ratio is not dependent on the time of sampling during the day (i.e., morning vs. night) (P> 0.1) and 2. the average within-subject biological variation in the 3HC/COT ratio is approximately 26%. These findings should be useful for designing large-scale population surveys to assess the variation in the metabolic rate of nicotine (via CYP2A6) in smokers.

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Subjects: Medical Toxicology ; Toxicology (Non-medical)

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