Quantitative assessment of exposure-response relationships for the efficacy and tolerability of varenicline for smoking cessation

Clinical Pharmacology and Therapeutics
P RavvaH M Faessel

Abstract

Population exposure-response analyses involving approximately 2,000 cigarette smokers provided an integrated understanding of dose, exposure, patient characteristics, and response relating to the efficacy and tolerability of varenicline for smoking cessation. Full models with a linear function of area under the concentration-time curve at steady state AUC(0-24)(ss) and covariate effects on the baseline probability of response were constructed. Logistic regression results consistently showed that the end-of-treatment abstinence rate increased with increasing varenicline exposure, from 38% at 0.5 mg b.i.d. to 56% at 1 mg b.i.d. (vs. 22% for placebo). Baseline smoking status and age were predictive of smoking cessation, whereas race and gender showed little or no influence. Nausea was the most common adverse event, with an incidence that was gender-related and that increased with varenicline exposure; at a dosage of 1 mg b.i.d. the predicted probability of nausea relative to placebo was 24 vs. 7% in male subjects and 40 vs. 14% in female subjects. The incidence of nausea also showed a decreasing trend with time.

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Citations

Jul 6, 2010·Pharmacoepidemiology and Drug Safety·Mira Harrison-Woolrych, Janelle Ashton
Oct 9, 2015·Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco·Sherry A McKeeAndrea H Weinberger
Jun 8, 2011·Expert Opinion on Pharmacotherapy·Jill M WilliamsJonathan Foulds
May 27, 2016·Journal of Social Work Practice in the Addictions·Natalie HemsingNancy Poole
Feb 26, 2011·Journal of Substance Abuse Treatment·Maria Caterina GrassiPaolo Nencini
Nov 20, 2013·Dementia and Geriatric Cognitive Disorders·Seong Yoon KimJanice Jacobsen
Nov 9, 2010·Clinical Pharmacokinetics·Hélène M FaesselAaron H Burstein
May 10, 2016·The Cochrane Database of Systematic Reviews·Kate CahillTim Lancaster
Jun 2, 2021·CPT: Pharmacometrics & Systems Pharmacology·Daryl J FediukWonkyung Byon

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