title: 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.
abstract: 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.
authors.affiliation: The Institute of Environmental Science and Research, Wellington, New Zealand. Rod.Lea@esr.cri.nz
authors.forename: Rod A
authors.initials: RA
authors.lastname: Lea
authors.forename: Stuart
authors.initials: S
authors.lastname: Dickson
authors.forename: Neal L
authors.initials: NL
authors.lastname: Benowitz
mesh_terms: D000704:Analysis of Variance; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D003367:Cotinine / Q000031:analogs & derivatives* / Q000378:metabolism*; D065637:Cytochrome P-450 CYP2A6; D003625:Data Collection; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009538:Nicotine / Q000378:metabolism*; D010865:Pilot Projects; D012463:Saliva / Q000378:metabolism*; D012907:Smoking
chemical_list: D015415:Biomarkers; C001381:hydroxycotinine; D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine