The pharmacological basis for metrifonate's favourable tolerability in the treatment of Alzheimer's disease

被引:11
作者
Schmidt, BH
Heinig, R
机构
[1] Troponwerke GmbH & Co KG, Bayer CNS Res, D-51063 Cologne, Germany
[2] Bayer AG, Clin Pharmacol, D-5600 Wuppertal, Germany
关键词
Alzheimer therapy; metrifonate; tolerability; DDVP; cholinesterase inhibition;
D O I
10.1159/000051194
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Metrifonate, through its pharmacologically active metabolite 2,2-dichlorovinyl dimethylphosphate (DDVP), is a long-acting cholinesterase inhibitor for the symptomatic treatment of mild-to-moderate Alzheimer's disease. Clinical studies with Alzheimer patients have demonstrated the favourable safety and tolerability profile of this drug. Metrifonate, at therapeutic doses for Alzheimer's disease, achieves high levels of cholinesterase inhibition, i.e. greater than or equal to 70%, without the need for dose escalation. This is a consequence of the low rate of fluctuation of enzyme activity during therapy with metrifonate. This, in turn, is due to the protracted hydrolytic transformation of metrifonate into DDVP, the resulting smooth onset of cholinesterase inhibition, and the subsequent long duration of action which far outlasts the presence of the active drug in the body. Both metrifonate and DDVP are rapidly metabolized and eliminated from the body. Further, their metabolism does not involve the cytochrome P450 system and both compounds show low plasma protein binding. These pharmacokinetic features account, at least in part, for the favourable safety and tolerability profile of metrifonate as they suggest a minimal risk of drug-drug interactions with other likely co-medications in the long-term therapy of Alzheimer patients.
引用
收藏
页码:15 / 19
页数:5
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