Pharmacokinetic-pharmacodynamic modeling of the effect of varenicline on nicotine craving in adult smokers.

Abstract

INTRODUCTION:

Varenicline has been shown to significantly reduce craving and several aspects of smoking reinforcement in clinical trials, compared with placebo. This is the first report describing the concentration-effect relationship of varenicline on relief of craving.

METHODS:

The pharmacokinetics (PK) and pharmacodynamics (PD) of a single 2mg dose of varenicline were investigated in 40 smokers in a randomized, crossover study comparing the effect of varenicline with placebo on ameliorating abstinence-and cue-induced craving and withdrawal symptoms. Subjects were asked to complete self-reported questionnaires (Smoking Urges Scale and Minnesota Nicotine Withdrawal Scale [MNWS]) and blood samples were simultaneously collected for measurement of varenicline concentrations. Only the data from the 4-hr postdose abstinence period (just prior to the cue session) were analyzed. Data were described by a 2-compartment PK model and a linear PD model with first-order onset/offset rate constants describing the placebo response "kinetics." Response was described as the net effect of the baseline, placebo, and drug responses.

RESULTS:

Varenicline significantly decreased mean craving score when compared with placebo and the magnitude of this response was related to varenicline concentration. The time-course and magnitude of both placebo and varenicline craving response were characterized by a large degree of unexplained variability. Simulations were used to illustrate the expected craving response over time and its associated random variability after chronic dosing.

CONCLUSIONS:

Craving reduction is associated with increased varenicline concentrations. The relatively rapid onset of this effect within 4 hr postdose suggests that, smokers may experience some craving relief after acute administration of varenicline.

• Authors: Patanjali Ravva, Marc R Gastonguay, Hélène M Faessel, Theodore C Lee, Raymond Niaura
• Journal: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco (Nicotine Tob Res) Vol. 17 Issue 1 Pg. 106-13 (Jan 2015) ISSN: 1469-994X [Electronic] England
• PMID: 25145377 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Benzazepines
• Nicotinic Agonists
• Quinoxalines
• Nicotine
• Varenicline

Topics

• Adolescent
• Adult
• Benzazepines (blood, pharmacokinetics, pharmacology)
• Craving (drug effects)
• Cross-Over Studies
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Nicotine (adverse effects)
• Nicotinic Agonists (blood, pharmacokinetics, pharmacology)
• Quinoxalines (blood, pharmacokinetics, pharmacology)
• Smoking (drug therapy)
• Smoking Cessation (methods)
• Surveys and Questionnaires
• Varenicline