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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 30, Issue 6, July/August 2006,
pp.386-389
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[1], Stuart Dickson[1], and Neal L. Benowitz[2]
[1]The Institute of Environmental Science and Research, Wellington, New Zealand
and
[2]Division of Clinical Pharmacology and Experimental Therapeutics, Departments
of Medicine, Psychiatry and Biopharmaceutical Sciences, University of California,
San Francisco, California
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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