Pharmacokinetics, safety, and tolerability following multiple oral doses of varenicline under various titration schedules in elderly nonsmokers

• Published in: Journal of clinical pharmacology Vol. 51; no. 4; p. 492
• Main Authors: Zhao, Qinying, Schwam, Elias, Fullerton, Terence, O'Gorman, Melissa, Burstein, Aaron H
• Format: Journal Article
• Language: English
• Published: England 01.04.2011
• Subjects: Administration, Oral; Aged; Benzazepines - administration & dosage; Benzazepines - adverse effects; Benzazepines - pharmacokinetics; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Half-Life; Humans; Male; Nicotinic Agonists - administration & dosage; Nicotinic Agonists - adverse effects; Nicotinic Agonists - pharmacokinetics; Placebos; Quinoxalines - administration & dosage; Quinoxalines - adverse effects; Quinoxalines - pharmacokinetics; Single-Blind Method; Varenicline
• ISSN: 1552-4604
• DOI: 10.1177/0091270010370461

This study was designed to investigate the multiple-dose pharmacokinetics, safety, and tolerability of the selective α4β2 nicotinic acetylcholine partial agonist, varenicline, in elderly (65-85 years old) nonsmokers. Fifty male and female subjects with normal renal function for their age were randomized to receive varenicline or placebo once or twice daily for 3 weeks in an investigator- and subject-blinded parallel-group design. Treatment regimens included weekly titration (n = 14; days 1-7, 0.5 mg once daily; days 8-14, 0.5 mg twice daily; days 15-21, 1 mg twice daily); 2-week twice-daily titration (n = 13; days 1-14, 0.5 mg once daily; days 15-21, 0.5 mg twice daily); 2-week once-daily titration (n = 13; days 1-14, 0.5 mg once daily; days 15-21, 1 mg once daily); and placebo (n = 10). Approximate dose-proportional increases in systemic exposure of varenicline at steady state, based on maximum concentration and area under the plasma concentration-time curve over the 24-hour period at steady state, were observed across the dose range of 0.5 to 2 mg/d. Median time to maximum concentration was 3 hours. Mean elimination half-life was estimated to be approximately 24 to 32 hours and independent of dose. Varenicline was considered to be safe and well tolerated in this elderly nonsmoking population.