PLASMA-CONCENTRATIONS AND PHARMACOKINETICS OF IDEBENONE AND ITS METABOLITES FOLLOWING SINGLE AND REPEATED DOSES IN YOUNG-PATIENTS WITH MITOCHONDRIAL ENCEPHALOMYOPATHY

Objective: The pharmacokinetics and tolerance of idebenone after singl e or repeated doses have been studied in young patients with mitochond rial encephalomyopathy. Results: No significant adverse effects were n oted. In 3 out of 7 patients idebenone induced overall stimulation and improvement in arousal. Plasma concentrations of idebenone and its ma in metabolites were determined and the pharmacokinetic parameters of i debenone after single and repeated doses were estimated. During the si ngle dose study, the mean plasma concentrations of idebenone and its m ain metabolites and mean pharmacokinetic parameters were comparable to published results (C-max = 452.2 ng . ml(-1), t(max) = 2.3 h, AUC = 2 6 mu g . ml(-1). h, t(1/2 beta) = 16.5 h). During the repeated doses s tudy, no significant difference was found between mean residual plasma concentrations of idebenone on Day 2 (47 ng . ml(-1)) and Day 5 (70.6 ng . ml(-1)), and mean t(1/2 beta) Of idebenone after the single and after repeated dose studies, i.e., there was no evidence of accumulati on. Although idebenone did not appear to accumulate during this study, the coadministration of anticonvulsants, often prescribed during mito chondrial encephalomyopathy, can affect its pharmacokinetics.