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Pharmacokinetic analysis of nicotine and its metabolites (cotinine and trans-3′-hydroxycotinine) in male Sprague-Dawley rats following nose-only inhalation, oral gavage, and intravenous infusion of nicotine
Abstract Nicotine is an alkaloid found in tobacco. Human exposure to nicotine primarily occurs through the use of tobacco products. To date, limited nicotine pharmacokinetic data in animals have been reported. This study exposed male Sprague-Dawley rats to vehicle (and/or air) or 4 doses of nicotine...
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Published in: | Toxicological sciences 2024-12, Vol.202 (2), p.196-209 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | Abstract
Nicotine is an alkaloid found in tobacco. Human exposure to nicotine primarily occurs through the use of tobacco products. To date, limited nicotine pharmacokinetic data in animals have been reported. This study exposed male Sprague-Dawley rats to vehicle (and/or air) or 4 doses of nicotine via nose-only inhalation (INH), oral gavage (PO), and intravenous (IV) infusion. Plasma, 6 tissues (brain, heart, lung, liver, kidney, and muscle), and urine were collected at multiple timepoints from 5 min to 48 h post-dose. The concentrations of nicotine, cotinine, and trans-3′-hydroxycotinine (3-OH-cotinine) were determined, and the pharmacokinetic profiles were compared among the 4 doses for each route. The results indicated that after single nicotine dose, nicotine bioavailability was 53% via PO. Across all the administration routes and doses, nicotine was quickly distributed to all 6 tissues; kidney had the highest nicotine and cotinine levels, and the lung had the highest 3-OH-cotinine levels; nicotine was metabolized extensively to cotinine and cotinine was metabolized to a lesser extent to 3-OH-cotinine; the elimination of plasma nicotine, cotinine, and 3-OH-cotinine followed first-order kinetics; plasma nicotine had a shorter half-life than cotinine or 3-OH-cotinine; the half-lives of plasma nicotine, cotinine, and 3-OH-cotinine were dose- and route-independent; and nicotine and cotinine were major urinary excretions followed by 3-OH-cotinine. Nicotine, cotinine, and 3-OH-cotinine levels in plasma, tissues, and urine exhibited dose-dependent increases. These study findings improve our understanding of the pharmacokinetics of nicotine, cotinine, and 3-OH-cotinine across different routes of exposure. |
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ISSN: | 1096-6080 1096-0929 1096-0929 |
DOI: | 10.1093/toxsci/kfae120 |