Pharmacokinetic and Pharmacodynamic Properties of Cholinesterase Inhibitors Donepezil, Tacrine, and Galantamine in Aged and Young Lister Hooded Rats
Pharmacokinetic and Pharmacodynamic Properties of Cholinesterase Inhibitors Donepezil, Tacrine, and Galantamine in Aged and Young Lister Hooded Rats
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DOI：
10.1124/dmd.110.035964
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发表时间：
2011-03-01
影响因子：
3.9
通讯作者：
Browne, Edward R.
中科院分区：
文献类型：
--
作者：
Goh, Catherine W.;Aw, Chiu Cheong;Browne, Edward R.
随着年龄的增长，生理变化可能会改变药理反应。在老年 Lister 罩盖大鼠模型中研究了用于治疗阿尔茨海默病的胆碱酯酶抑制剂 (ChEI)、多奈哌齐、他克林和加兰他敏的药代动力学/药效学特性。老年（30 个月大）和年轻（7 个月大）大鼠的静脉和口服 6 小时血液采样曲线显示，药代动力学变化与人类相似，加兰他敏的 C-max 增加约 40%，多奈哌齐的 t(1/2)（1.4 倍）和平均停留时间（1.5 倍）延长。他克林的分布随着年龄的增长而保持不变，对于所有测试的药物，老年大鼠的浓度-时间曲线下面积和清除率与年轻大鼠相似，生物利用度也是如此。年老大鼠表现出药效敏感性增加的趋势（
Physiological alterations that may change pharmacological response accompany aging. Pharmacokinetic/pharmacodynamic properties of cholinesterase inhibitors (ChEIs) used in the treatment of Alzheimer's disease, donepezil, tacrine, and galantamine, were investigated in an aged Lister hooded rat model. Intravenous and oral 6-h blood sampling profiles in old (30 months old) and young (7 months old) rats revealed pharmacokinetic changes similar to those in humans with an approximately 40% increase in C-max of galantamine and prolonged t(1/2) (1.4-fold) and mean residence time (1.5-fold) of donepezil. Tacrine disposition was maintained with age, and area under the concentration-time curve and clearance in old rats were similar to those in young rats for all drugs tested as was bioavailability. Old rats showed a trend of increased pharmacodynamic sensitivity (