Pharmacokinetics, safety, and tolerability following multiple oral doses of varenicline under various titration schedules in elderly nonsmokers.
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.
Zhao
Qinying
Q
Department of Clinical Pharmacology in Research Unit, Pfizer Inc, New London, Connecticut, USA. Qinying.Zhao@pfizer.com
Schwam
Elias
E
Fullerton
Terence
T
O'Gorman
Melissa
M
Burstein
Aaron H
AH
D000284:Administration, Oral; D000368:Aged; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D010919:Placebos; D011810:Quinoxalines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D016037:Single-Blind Method; D000068580:Varenicline
D001552:Benzazepines; D018722:Nicotinic Agonists; D010919:Placebos; D011810:Quinoxalines; D000068580:Varenicline