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Nicotine and cotinine elimination pharmacokinetics in smokers and nonsmokers
Abstract
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 micrograms/kg/min x 30 minutes) and in 11 nonsmokers (0.5 micrograms/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.
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“The half-life of nicotine is approximately 2.5 hours in adults15 and 9–11 hours in newborns,16--one of the shortest half-lives of drugs used during pregnancy17.”
From Maternal Smoking during Pregnancy and Newborn Neurobehavior: Effects at 10 to 27 Days (2009) · cites this paper as [15]
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Metabolism and Disposition Kinetics of Nicotine
Hukkanen, J., Jacob, P., & Benowitz, N. L. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.1.3 · Cited by 1,583
“However, we found that the clearance of nicotine was significantly slower in cigarette smokers compared with nonsmokers (Benowitz and Jacob, 1993).”
BackgroundSelf-citationNicotine Chemistry, Metabolism, Kinetics and Biomarkers
Benowitz, N. L., Hukkanen, J., & Jacob, P. (2009) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-69248-5_2 · Cited by 1,424
“However, we found that the clearance of nicotine was significantly slower in cigarette smokers than in nonsmokers (Benowitz and Jacob 1993).”
BackgroundSelf-citationCotinine as a Biomarker of Environmental Tobacco Smoke Exposure
Benowitz, N. L. (1996) · Epidemiologic Reviews · doi:10.1093/oxfordjournals.epirev.a017925 · Cited by 1,029
“Finally, the particular form of the drug metabolizing enzyme CYP450, forms that are induced by cigarette smoking, are not the same ones that are believed to be involved in the metabolism of nicotine or cotinine (35).”
BackgroundInfluentialSelf-citationDrug Interactions with Tobacco Smoking
Zevin, S., & Benowitz, N. L. (1999) · Clinical Pharmacokinetics · doi:10.2165/00003088-199936060-00004 · Cited by 711
Self-citationBiomarkers of environmental tobacco smoke exposure.
Benowitz, N. L. (1999) · Environmental Health Perspectives · doi:10.1289/ehp.99107s2349 · Cited by 389
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Metadata
- Authors
- Benowitz, N. L., & Jacob III, P.
- Affiliations
- San Francisco General Hospital (US)
- Corresponding author
- Benowitz, Neal L
- Venue
- Clinical Pharmacology and Therapeutics
- Publisher
- Wiley
- Published
- 1993-03
- Volume
- 53
- Issue
- 3
- Pages
- 316-323
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- OpenAlex
- W1983882432
- Cited by
- 232
- References
- 0
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 7 · 2017: 6 · 2016: 4 · 2015: 8 · 2014: 8 · 2013: 8 · 2012: 18
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50da001696-18, 2m01rr000083-41)
- National Institute on Drug Abuse (DA02277, DA-01696)
- National Center for Research Resources (RR 00083)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- nicotine, cotinine, pharmacokinetics, smokers, non-smokers, nicotine clearance, nicotine metabolism, metabolic tolerance, dose escalation, passive smoking
- MeSH terms
- Adult, Cotinine, Deuterium, Dose-Response Relationship, Drug, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Nicotine, Regression Analysis, Smoking
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