Trans‐3′‐hydroxycotinine: Disposition kinetics, effects and plasma levels during cigarette smoking

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 response...

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Bibliographic Details
Published in:British journal of clinical pharmacology 2001-01, Vol.51 (1), p.53-59
Main Authors: Benowitz, N. L., Jacob, P.
Format: Article
Language:English
Subjects:
3′‐hydroxycotinine
Adult
Affect - drug effects
Biological and medical sciences
cotinine
Cotinine - analogs & derivatives
Cotinine - blood
Cotinine - pharmacokinetics
Female
Half-Life
Humans
Infusions, Intravenous
Main Paper
Male
Medical sciences
metabolism
Middle Aged
nicotine
Nicotine - blood
pharmacodynamics
pharmacokinetics
smoking
Smoking - blood
Smoking - metabolism
Tissue Distribution
tobacco
Tobacco, tobacco smoking
Toxicology
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Summary: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 µg kg−1 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 min−1 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.
ISSN:0306-5251
1365-2125
DOI:10.1046/j.1365-2125.2001.01309.x