Pharmacokinetics and metabolism of idebenone in healthy male subjects.

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.