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Nicotine And Cotinine Elimination Pharmacokinetics In Smokers And Nonsmokers

N. Benowitz, P. Jacob
Published 1993 · Chemistry, Medicine

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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 µg/kg/min × 30 minutes) and in 11 nonsmokers (0.5 µg/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.
This paper references
Effect of nicotine treatment on the metabolism of nicotine in the mouse liver in vitro.
T. Stålhandske (1970)
The effect of smoking on nicotine metabolism in vivo in man
A. H. Beckett (1971)
Nicotine Inhibition of the Metabolism of 3,4-Benzopyrene, a Carcinogen in Tobacco Smoke
R. P. Weber (1974)
Comparison of the effect of carbon monoxide and of hypoxic hypoxia. I. In vivo metabolism, distribution and action of hexobarbital.
R. Roth (1976)
Biochemical markers.
J. Glass (1981)
Nicotyrine inhibits in vivo metabolism of nicotine without increasing its toxicity.
T. Stålhandske (1982)
Interindividual variability in the metabolism and cardiovascular effects of nicotine in man.
N. Benowitz (1982)
Smoking‐induced changes in nicotine disposition: Application of a new HPLC assay for nicotine and its metabolites
G. A. Kyerematen (1982)
Heterogeneity of hepatic nicotine oxidase.
H. Nakayama (1982)
hepatic nicotine oxidase
DE Williams (1982)
ES. Smoking-induced changes in nicotine disposition: application of a new HPLC assay for nicotine and its metabolites. CL1N PHARMACOL THER 1982;32:769-80
ML (1982)
Biochemical markers of smoke absorption and self reported exposure to passive smoking.
M. Jarvis (1984)
Department of Health and Human Services. The health consequences of involuntary smoking. A report of the Surgeon General. Washington: DHHS Public Health Service
Influence of tobacco abstinence on the disposition kinetics and effects of nicotine
Belle L Lee (1987)
Elimination of cotinine from body fluids: implications for noninvasive measurement of tobacco smoke exposure.
M. Jarvis (1988)
Synthesis of optically pure deuterium‐labelled nicotine, nornicotine and cotinine
P. Jacob (1988)
Drug therapy. Pharmacologic aspects of cigarette smoking and nicotine addiction.
N. Benowitz (1988)
Elimination of cotinine from body fluids: disposition in smokers and nonsmokers.
N. Haley (1989)
Microsomal nicotine metabolism: a comparison of relative activities of six purified rabbit cytochrome P-450 isozymes.
G. Mccoy (1989)
The role of cytochromes P-450 and flavin-containing monooxygenase in the metabolism of (S)-nicotine by rabbit lung.
D. E. Williams (1990)
Disposition of nicotine and eight metabolites in smokers and nonsmokers: Identification in smokers of two metabolites that are longer lived than cotinine
Gabriel A Kyerematen (1990)
Metabolism of nicotine by hepatocytes.
G. A. Kyerematen (1990)
Metabolism of nicotine by rat liver cytochromes P-450. Assessment utilizing monoclonal antibodies to nicotine and cotinine.
D. Hammond (1991)
Selected ion monitoring method for determination of nicotine, cotinine and deuterium-labeled analogs: absence of an isotope effect in the clearance of (S)-nicotine-3',3'-d2 in humans.
P. Jacob (1991)
Stable isotope studies of nicotine kinetics and bioavailability
N. Benowitz (1991)
Stable isotope method for studying transdermal drug absorption: The nicotine patch
N. Benowitz (1991)
Metabolism of nicotine by human liver microsomes: stereoselective formation of trans-nicotine N'-oxide.
J. Cashman (1992)
Nicotine metabolism by cDNA-expressed human cytochrome P-450s
A. M. Flammang (1992)
Smoking and drug metabolism.
E. McGuffey (1993)
How tobacco produces drug dependence
JE Henningfield

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E. Domino (2019)
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Takanobu Matsuzaki (2019)
Determination of nicotine content in teeth submitted to prophylaxis and in-office bleaching by gas chromatography–mass spectrometry (GC-MS)
J. D. de Geus (2018)
Brain derived neurotrophic factor (BDNF), its tyrosine kinase receptor B (TrkB) and nicotine.
R. Machaalani (2018)
Biomarkers of Exposure to Secondhand and Thirdhand Tobacco Smoke: Recent Advances and Future Perspectives
Sònia Torres (2018)
Nicotine-N′-Oxidation by Flavin Monooxygenase Enzymes
Yadira X Perez-Paramo (2018)
E-cigarettes: Impact of E-liquid Components and Device Characteristics on Nicotine Exposure
E. DeVito (2018)
Protocol to assess the impact of tobacco-induced volatile organic compounds on cardiovascular risk in a cross- sectional cohort: Cardiovascular Injury due to Tobacco Use study
R. Keith (2018)
Population pharmacokinetic model of transdermal nicotine delivered from a matrix‐type patch
Matthew W Linakis (2017)
Racemic Salsolinol and its Enantiomers Act as Agonists of the μ-Opioid Receptor by Activating the Gi Protein-Adenylate Cyclase Pathway
Pablo Berríos-Cárcamo (2017)
Biomarkers of exposure to new and emerging tobacco delivery products.
S. Schick (2017)
One-Year Smoking Trajectories Among Established Adult Smokers With Low Baseline Motivation to Quit
A. Mathew (2017)
Predictors of Variation in CYP2A6 mRNA, Protein, and Enzyme Activity in a Human Liver Bank: Influence of Genetic and Nongenetic Factors
J. Tanner (2017)
Rapid detection of nicotine from breath using desorption ionisation on porous silicon.
T. Guinan (2017)
Title : Predictors of variation in CYP 2 A 6 mRNA , protein , and enzyme activity in a human liver bank : influence of genetic and non-genetic factors
Julie-Anne Tanner (2016)
Brain Orexin Receptors and Nicotine
R. Machaalani (2016)
Evaluation of Serum Cotinine Cut-Off to Distinguish Smokers From Nonsmokers in the Korean Population
K. Ko (2016)
Self‐reported Tobacco use does not correlate with carcinogen exposure in smokers with head and neck cancer
S. Khariwala (2015)
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