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- Title
Pharmacokinetic-pharmacodynamic modeling of the effect of varenicline on nicotine craving in adult smokers.
- Authors
Ravva, Patanjali; Gastonguay, Marc R; Faessel, Hélène M; Lee, Theodore C; Niaura, Raymond
- Abstract
<bold>Introduction: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
CROSSOVER trials; DESIRE; HETEROCYCLIC compounds; NICOTINE; QUESTIONNAIRES; SMOKING; SMOKING cessation; RANDOMIZED controlled trials; BLIND experiment; NICOTINIC agonists; PHARMACODYNAMICS
- Publication
Nicotine & Tobacco Research, 2015, Vol 17, Issue 1, p106
- ISSN
1462-2203
- Publication type
journal article
- DOI
10.1093/ntr/ntu154