Pharmacokinetics and metabolism of idebenone in healthy male subjects
Pharmacokinetics and metabolism of idebenone in healthy male subjects
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DOI：
10.1007/s00228-008-0596-1
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发表时间：
2009-05-01
影响因子：
2.9
通讯作者：
Drewe, Juergen
中科院分区：
文献类型：
--
作者：
Bodmer, Michael;Vankan, Pierre;Drewe, Juergen
艾地苯醌是泛醌的合成类似物，可能有益于治疗弗里德赖希共济失调。由于在以前的药代动力学试验中只研究了较低剂量，因此本研究的目的是评估艾地苯醌在高达2，250 mg/day的较高剂量下的药代动力学。在这项开放、随机试验中，25名健康男性受试者首先接受150 mg或750 mg艾地苯醌的单次口服剂量，艾地苯醌及其代谢产物迅速出现在血浆中。超过99%的母体艾地苯醌被代谢，表明高首过效应。母体艾地苯醌及其代谢产物的C-max和AUC（0-t）值以剂量比例方式增加。多次给药后几乎没有母体药物或代谢物的蓄积。艾地苯醌在每日剂量高达2，250 mg时表现出剂量依赖性药代动力学。在6/14例受试者中观察到轻度至中度的不良事件。
Idebenone is a synthetic analogue of ubiquinone that may be beneficial in the treatment of Friedreich's ataxia. Since in previous pharmacokinetic trials only lower doses were studied, it was the aim of this study to evaluate the pharmacokinetics of idebenone in higher doses of up to 2,250 mg/day.In this open, randomized trial, 25 healthy male subjects received first either a single oral dose of 150 mg or 750 mg of idebenone, then the same dose given at 8-h intervals for 14 days.Idebenone and its metabolites appeared in the plasma quickly. Over 99% of parent idebenone was metabolized, indicating a high first-pass effect. C-max and AUC(0-t) values for parent idebenone and its metabolites increased in a dose-proportional manner. There was virtually no accumulation of parent drug or metabolites following multiple dosing.Idebenone exhibited dose-dependent pharmacokinetics in daily doses up to 2,250 mg. In 6/14 subjects, adverse events of mild to moderate severity were observed.