Donepezil: a review.
Donepezil: a review.
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DOI：
10.1517/17425255.1.3.527
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发表时间：
2005-10-01
影响因子：
4.3
通讯作者：
Seltzer, Ben
中科院分区：
文献类型：
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作者：
Seltzer, Ben
多奈哌齐是一种选择性乙酰胆碱酯酶抑制剂，广泛用于治疗阿尔茨海默病 (AD)。它已被证明对轻度、中度和重度 AD、血管性痴呆和帕金森病相关痴呆有益。多奈哌齐从肠道缓慢但完全吸收，在 3-4 小时内达到血浆峰值水平，每日给药可在 15-21 天内达到稳态浓度。在相对较窄的范围内，剂量和药效学效应之间存在线性关系，以红细胞乙酰胆碱酯酶抑制和临床疗效来衡量。多奈哌齐主要以原形通过尿液排出，但也有肝脏代谢；它的一些代谢物可能具有活性。尽管96%与血浆蛋白结合，但它与其他药物几乎没有相互作用，5毫克剂量可以安全地给予轻至中度肝病和肾病患者。副作用主要是其拟胆碱作用机制造成的，通常是轻微且短暂的。尽管多奈哌齐最初是为了抑制神经递质乙酰胆碱的分解而开发的，作为 AD 的对症治疗，但最近的研究提出了该药物对 AD 发病机制产生其他影响的可能性。
Donepezil is a selective acetylcholinesterase inhibitor that is widely prescribed for Alzheimer's disease (AD). It has been shown to be of benefit in mild, moderate and severe stages of AD, vascular dementia and dementia associated with Parkinson's disease. Donepezil is absorbed slowly, but completely, from the gut, reaching peak plasma levels in 3-4 h and, with daily dosing, steady-state concentration in 15-21 days. Within a relatively narrow range, there is a linear relationship between dose and pharmacodynamic effects, measured as red blood cell acetylcholinesterase inhibition and clinical efficacy. Donepezil is principally excreted unchanged in the urine, but there is also hepatic metabolism; some of its metabolites may be active. Despite being 96% bound to plasma proteins, it has few interactions with other drugs, and the 5-mg dose can be given safely to patients with mild-to-moderate hepatic and renal -disease. Side effects, which are mainly a consequence of its cholinomimetic mechanism of action, are usually mild and transient. Although donepezil was originally developed to inhibit the breakdown of the neurotransmitter acetylcholine as symptomatic therapy for AD, recent studies raise the possibility of other effects this drug has on the pathogenesis of AD.