Nicotine metabolism and elimination kinetics in newborns
Abstract
OBJECTIVE: To characterize the presence of and elimination kinetics of nicotine and its metabolites in newborns. METHODS: Blood samples from 13 newborns were collected during the first day of life and analyzed for nicotine and cotinine. Single daily urine samples were collected from nine newborns for up to 7 days and analyzed by gas chromatography-mass spectrometry for nicotine, cotinine, 3'-hydroxycotinine, and their conjugates. NONMEM was used to determine population half-life values. RESULTS: Blood and urine data gave similar results for nicotine and cotinine elimination kinetics. The elimination half-life for nicotine was 11.2 hours (95% confidence interval [CI], 8.0 to 18.9) based on blood data and 9.0 hours (95% CI, 7.0 to 12.4) based on urine data. The elimination half-life for cotinine was 16.3 hours (95% CI, 12.4 to 23.9) based on blood data and was 22.8 hours (95% CI, 19.5 to 25.8) based on urine data. The elimination half-lives for the other metabolites were 13 hours for conjugated nicotine; 19.8 hours for conjugated cotinine; 18.8 hours for 3'-hydroxycotinine; and 19.4 hours for conjugated 3'-hydroxycotinine. The half-life of nicotine is three to four times longer in newborns than in adults, whereas the half-life of cotinine is similar in newborns and adults. CONCLUSIONS: In adults, CYP2A6 is the predominant enzyme responsible for the metabolism of both nicotine and cotinine. The prolonged elimination of nicotine but not of cotinine in the newborn compared with that in the adult may be a result of different newborn CYP2A6 enzymatic substrate specificity, low CYP2A6 activity with another enzyme that is primarily responsible for cotinine metabolism, or differences in tissue distribution.
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The half-life of nicotine is 9-11 hours in newborns.
“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 [16]
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- Authors
- Dempsey, D.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Dempsey, D
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2000-05
- Volume
- 67
- Issue
- 5
- Pages
- 458-465
- ISSN
- 0009-9236 (ISSN-L)
- OpenAlex
- W2152172857
- Cited by
- 112
- References
- 22
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 11 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 7 · 2014: 5 · 2013: 4 · 2012: 6
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01da009761-02, 5p50da001696-18)
- National Institute on Drug Abuse (DA02277, DA-01696, DA09761)
- 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 metabolism, cotinine, 3-hydroxycotinine, elimination kinetics, neonates, elimination half-life, CYP2A6, urinary biomarkers, tissue distribution, neonatal pharmacokinetics
- MeSH terms
- Aryl Hydrocarbon Hydroxylases, Cotinine, Cytochrome P-450 Enzyme System, Female, Half-Life, Humans, Mixed Function Oxygenases, Infant, Newborn, Male, Gas Chromatography-Mass Spectrometry, Nicotine, Prospective Studies, Cytochrome P-450 CYP2A6
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