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 adults.
“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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Joya, X., Manzano, C., Álvarez, A.-T., Mercadal‐Hally, M., Torres, F., Salat‐Batlle, J., & García‐Algar, Ó. (2014) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph110707261 · Cited by 45 · see citing works
“NIC presents a half-life of approximately 2–3 h in blood, followed by urinary excretion [60].”
BackgroundInvestigating the impact of nicotine on executive functions using a novel virtual reality assessment
Jansari, A. S., Froggatt, D., Edginton, T. L., & Dawkins, L. (2012) · Addiction · doi:10.1111/add.12082 · Cited by 44 · see citing works
“A cigarette, by way of comparison, can increase plasma nicotine levels by approximately 14 ng/mL (41).”
BackgroundEstimating tar and nicotine exposure: Human smoking versus machine generated smoke yields
Charles, F. S., Kabbani, A. A., & Borgerding, M. F. (2009) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2009.08.011 · Cited by 46 · see citing works
Behavioural Pharmacology and Neurobiology of Nicotine Reward and Dependence
Chiara, G. D. (2000) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-57079-7_24 · Cited by 43 · see citing works
Effects of postnatal nicotine exposure on apoptotic markers in the developing piglet brain
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Dorne, J. L. C. M., Walton, K., & RENWICK, A. G. (2003) · Food and Chemical Toxicology · doi:10.1016/j.fct.2003.10.003 · Cited by 40 · see citing works
Winkelmann, B. R., Boehm, B. O., Nauck, M., Kleist, P., März, W., Verho, N. K., Ranjith, N., & KNEISSL, G. D. (2001) · Current Medical Research and Opinion · doi:10.1185/030079901317010801 · Cited by 45 · see citing works
The interaction of cigarette smoking and antioxidants. Part III: ascorbic acid.
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Biomarkers Derived from Nicotine and its Metabolites: A Review
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“The disposition pharmacokinetics of nicotine and metabolism are dose-independent (90).”
InfluentialClinical pharmacology of oral cotinine
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Self-citationMetabolism and biochemical effects of nicotine for primary care providers
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BackgroundHuman CYP2A6 is regulated by nuclear factor-erythroid 2 related factor 2
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Uses and abuses of cotinine as a marker of tobacco smoke exposure
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- 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 › Physiology › 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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