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Pharmacokinetics, Safety, and Tolerability Following Multiple Oral Doses of Varenicline Under Various Titration Schedules in Elderly Nonsmokers
Author(s) -
Zhao Qinying,
Schwam Elias,
Fullerton Terence,
O'Gorman Melissa,
Burstein Aaron H.
Publication year - 2011
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270010370461
Subject(s) - tolerability , pharmacokinetics , varenicline , medicine , placebo , anesthesia , population , area under the curve , crossover study , pharmacology , adverse effect , nicotine , alternative medicine , environmental health , pathology
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.