title: Pharmacokinetics, safety, and tolerability after single and multiple oral doses of varenicline in elderly smokers.
abstract: Varenicline is a novel selective alpha4beta2 nicotinic acetylcholine partial agonist developed for smoking cessation. This study investigated the single- and multiple-dose pharmacokinetics, safety, and tolerability of varenicline in elderly (> or = 65 years) smokers. Twenty-four elderly smokers with normal renal function for their age (estimated creatinine clearance > or = 70 mL/min) received varenicline 1 mg once daily (n = 8) or placebo (n = 4) for 7 days, or 1 mg twice daily (n = 8) or placebo (n = 4) for 6 days with a single dose on day 7 in a double-blind, parallel group and placebo-controlled design. There was no evidence of concentration- or time-dependent changes in varenicline pharmacokinetics upon repeat dosing. Once- and twice-daily dosing was associated with an approximate 2-fold and 3-fold increase, respectively, in systemic exposure to varenicline. Varenicline was well tolerated; all adverse events reported were mild to moderate in intensity. Thus, no dose adjustment is necessary based on age alone.
authors.affiliation: Department of Medical and Developmental Sciences, Pfizer Global Research and Development, Groton/New London Labs, MS8260-2505, Groton, CT 06340, USA.
authors.forename: Aaron H
authors.initials: AH
authors.lastname: Burstein
authors.forename: Terence
authors.initials: T
authors.lastname: Fullerton
authors.forename: David J
authors.initials: DJ
authors.lastname: Clark
authors.forename: Hélène M
authors.initials: HM
authors.lastname: Faessel
mesh_terms: 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; D006801:Humans; D008297:Male; D011810:Quinoxalines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D011978:Receptors, Nicotinic / Q000378:metabolism; D016540:Smoking Cessation / Q000379:methods; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D011810:Quinoxalines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D000068580:Varenicline