Trans‐3′‐hydroxycotinine: Disposition kinetics, effects and plasma levels during cigarette smoking
Open accessAbstract
AIMS: (3'R,5'S)-trans-3'-hydroxycotinine (3-HC) is a major metabolite of nicotine. The aim of this study was to characterize the disposition kinetics of 3-HC in healthy smokers, including metabolism to (3'R,5'S)-trans-3'-hydroxycotinine glucuronide (3-HC-Gluc). We also studied pharmacologic responses to 3-HC and plasma levels of 3-HC in a group of smokers. METHODS: Eight cigarette smokers were studied on a clinical research ward. After 5 days of supervised nonsmoking, each subject received an intravenous infusion of 3-HC, 4 microg x kg(-1) x min(-1) for 60 min. Plasma and urine levels of 3-HC and 3-HC-Gluc and cardiovascular and subjective responses were examined. Plasma levels of 3-HC, nicotine, and cotinine were measured in 62 smokers on up to three occasions. RESULTS: The total plasma clearance of 3-HC averaged 1.3 ml x min(-1) x kg(-1), of which 63% was renal excretion of unchanged drug. An average of 29% of the dose was excreted as 3-HC-Gluc. 3-HC did not have nicotine-like cardiovascular effects. CONCLUSIONS: These findings extend our understanding of the quantitative nature of nicotine metabolism. Such data may be of use in quantitating human exposure to nicotine from tobacco and in studying individual variability in nicotine metabolism.
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Nicotine follows an inverted U-shaped dose-response curve, and smokers titrate intake to get rewarding effects while avoiding aversive effects of high doses.
“Nicotine follows an inverted U-shaped dose-response curve [18, 60], and smokers titrate their nicotine intake to experience the rewarding while avoiding the aversive effects produced by high nicotine doses [61–64].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [62]
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References 26 · Cited by 114
Research works printed but not linked: 6
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- Authors
- Benowitz, N. L., & Jacob, P.
- Affiliations
- San Francisco General Hospital (US)
- Corresponding author
- Benowitz, N. L.
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2001-01
- Volume
- 51
- Issue
- 1
- Pages
- 53-59
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC2014428
- OpenAlex
- W1791887780
- Cited by
- 114
- References
- 26
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 6 · 2012: 4
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- Funders
- Deutsches Krebsforschungszentrum
- National Institutes of Health (5p50da001696-18, 2m01rr000083-41, RR-00083)
- National Institute on Drug Abuse (DA02277, DA-01696, R01DA002277, R37DA002277)
- National Center for Research Resources (M01-RR000083, RR 00083)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- trans-3'-hydroxycotinine, nicotine metabolites, cotinine, nicotine metabolism, disposition kinetics, plasma clearance, renal excretion, glucuronidation, cardiovascular effects, plasma nicotine levels, cigarette smoking, tobacco smoke exposure
- MeSH terms
- Adult, Affect, Cotinine, Female, Half-Life, Humans, Infusions, Intravenous, Male, Middle Aged, Nicotine, Smoking, Tissue Distribution
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