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Nicotine and cotinine elimination pharmacokinetics in smokers and nonsmokers
Author(s) -
Benowitz Neal L,
Jacob Peyton
Publication year - 1993
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1993.27
Subject(s) - cotinine , nicotine , pharmacokinetics , metabolite , pharmacology , medicine , disposition , tobacco smoke , physiology , chemistry , psychology , social psychology , environmental health
Published research suggests that smokers metabolize nicotine and its major metabolite cotinine more rapidly than nonsmokers. To evaluate this possibility, we studied the disposition pharmacokinetics of intravenous deuterium‐labeled nicotine in 11 smokers (administered 2.0 and 0.5 µg/kg/min × 30 minutes) and in 11 nonsmokers (0.5 µg/kg/min). Smokers did not metabolize nicotine more rapidly; the clearance of nicotine normalized for body weight was significantly slower in smokers than in nonsmokers. Cotinine elimination rates were similar in the two groups. The disposition pharmacokinetics of nicotine was similar for the low and high doses in the smokers, indicating that metabolism is dose‐independent. Our findings argue against “metabolic tolerance” as a mechanism for the dose escalation observed in smokers after initiation of smoking. Our findings suggest that nicotine and cotinine kinetic parameters for smokers may be extrapolated to nonsmokers for estimating exposures to environmental tobacco smoke in nonsmokers. Clinical Pharmacology and Therapeutics (1993) 53, 316–323; doi: 10.1038/clpt.1993.27