Metabolism of nicotine to cotinine studied by a dual stable isotope method
Abstract
Objectives (1) To determine the disposition kinetics of nicotine and cotinine, including the fractional conversion of nicotine to cotinine, (2) to compare the disposition kinetics of deuterium-labeled and unlabeled cotinine, and (3) to develop a pharmacokinetically based method for estimating daily intake of nicotine from cigarette smoking. Study design Twenty cigarette smokers received a combined infusion of deuterium-labeled nicotine (d2) and cotinine (d4). Six nonsmokers received a combined infusion of unlabeled cotinine, cotinine-d2 and cotinine-d4. Daily intake of nicotine was estimated with use of the plasma cotinine concentration during ad libitum smoking, clearance of labeled cotinine, and fractional conversion of nicotine to cotinine. Results The kinetics of labeled versus unlabeled cotinine and of cotinine in smokers versus nonsmokers were similar. On average, 72% of nicotine was converted to cotinine, with a range from 55% to 92%. Subjects with lower clearances of nicotine had lower fractional conversion of nicotine to cotinine, indicating that this is the most rapid of the proximate metabolic pathways for nicotine. The equation for estimating daily intake of nicotine from smoking was: Dnic (mg/24 hr) = K x (Plasma Cot) (ng/ml), where K averaged 0.08, with a range from 0.047 to 0.102. Individual variability in the clearance of cotinine (coefficient of variation, 27.5%) accounts for more of the variability in K than does variability in the fractional conversion of n…
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The T1/2 values are in line with the reported nicotine plasma elimination half-life.
“in line with the reported nicotine plasma elimination half-life [41].”
From A Randomised Study to Investigate the Nicotine Pharmacokinetics of Oral Nicotine Pouches and a Combustible Cigarette (2022) · cites this paper as [41]
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- Authors
- Benowitz, N. L., & Jacob, P.
- Venue
- Clinical Pharmacology and Therapeutics
- Publisher
- Wiley
- Published
- 1994-11
- Volume
- 56
- Issue
- 5
- Pages
- 483-493
- ISSN
- 0009-9236
- 1532-6535
- Cited by
- 387
- References
- 0
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