Pharmacokinetics, safety, and tolerability after single and multiple oral doses of varenicline in elderly smokers
Pharmacokinetics, safety, and tolerability after single and multiple oral doses of varenicline in elderly smokers
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DOI：
10.1177/0091270006291837
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发表时间：
2006-11-01
影响因子：
2.9
通讯作者：
Faessel, Helene M.
中科院分区：
文献类型：
--
作者：
Burstein, Aaron H.;Fullerton, Terence;Faessel, Helene M.
伐尼克兰是一种新型的选择性α 4 β 2烟碱乙酰胆碱部分激动剂，用于戒烟。本研究调查了老年（≥ 65岁）吸烟者单次和多次服用伐尼克兰的药代动力学、安全性和耐受性。24名老年吸烟者，其肾功能正常（估计肌酐清除率>= 70 mL/min），采用双盲、平行组和安慰剂对照设计，接受伐尼克兰1 mg每日1次（n = 8）或安慰剂（n = 4）治疗7天，或1 mg每日2次（n = 8）或安慰剂（n = 4）治疗6天，第7天单次给药。无证据表明重复给药后伐尼克兰的药代动力学发生浓度或时间依赖性变化。每日一次和每日两次给药分别使伐尼克兰全身暴露量增加约2倍和3倍。伐尼克兰耐受性良好;报告的所有不良事件的严重程度均为轻度至中度。因此，无需仅根据年龄调整剂量。
Varenicline is a novel selective alpha 4 beta 2 nicotinic acetylcholine partial agonist developed for smoking cessation. This study investigated the single- and multiple-dose pharmacokinetics, safety, and tolerability of varenicline in elderly (>= 65 years) smokers. Twenty-four elderly smokers with normal renal function for their age (estimated creatinine clearance >= 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.