Determinants of plasma concentrations of nicotine and cotinine during cigarette smoking and transdermal nicotine treatment |
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Authors: | S G Gourlay N L Benowitz A Forbes J J McNeil |
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Institution: | (1) UCSF Division of Clinical Pharmacology and Experimental Therapeutics, Room 375, UCSF Box 0898, San Francisco, CA 94143–0898, USA, US;(2) Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia, AU |
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Abstract: | Objective: Interindividual variability in plasma concentrations of nicotine and its proximate metabolite, cotinine, is considerable
during smoking and transdermal nicotine treatment, even among individuals taking in nominally similar doses of nicotine. This
report explores the determinants of this variability and the utility of baseline (smoking) plasma concentrations to predict
concentrations during transdermal nicotine treatment.
Methods: Data were analysed from a smoking cessation study (n = 466), and from a pharmacokinetic study (n = 12). Multiple regression models examined the relationships of plasma concentrations to individual characteristics such
as smoking pattern, absorbed dose of nicotine, and pharmacokinetic parameters.
Results: Plasma concentrations of nicotine and cotinine were highly variable in both studies. Indirect estimates of plasma clearance
(baseline plasma concentration divided by cigarettes per day) together with other factors could account for 18 to 33% of the
variability during transdermal nicotine treatment in the smoking cessation study. In contrast, 75 to 99% was accounted for
by direct measurements of plasma clearances and systemic dose of nicotine in the pharmacokinetic study.
Conclusion: Plasma concentrations of nicotine and cotinine during transdermal nicotine treatment are poorly predicted by clinical history
or baseline plasma concentrations. This is a result of inadequate characterisation of highly variable individual pharmacokinetic
parameters and absorbed dose of nicotine. Considering the interindividual variability of plasma nicotine and cotinine concentrations
together with the lack of clinical end-points for transdermal nicotine dosing, it seems logical to investigate the utility
of a therapeutic drug monitoring approach for transdermal nicotine treatment – particularly for high dose regimens (> 22 mg
per 24 hours).
Received: 7 May 1996 / Accepted in revised form: 21 August 1996 |
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Keywords: | Key words Transdermal Nicotine Plasma concen-trations Cotinine Smoking cessation |
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