idebenone and its metabolites following single and
repeated doses in young patients with mitochondrial encephalomyopathy.
Pisano P, Durand A, Autret E, Desnuelle C, Pinsard N, Serratrice G, Legout V
Pharmacologie Medicale et Clinique
CHU Timone Bt F-13385 Marseille, France.
Eur J Clin Pharmacol 1996;51(2):167-9
OBJECTIVE: The pharmacokinetics and tolerance of idebenone after single or
repeated doses have been studied in young patients with mitochondrial
RESULTS: No significant adverse effects
were noted. In 3 out of 7 patients idebenone induced overall stimulation and
improvement in arousal. Plasma concentrations of idebenone and its main
metabolites were determined and the pharmacokinetic parameters of idebenone
after single and repeated doses were estimated. During the single dose study,
the mean plasma concentrations of idebenone and its main metabolites and mean
pharmacokinetic parameters were comparable to published results (Cmax = 452.2
ng.ml-1, tmax = 2.3 h, AUC = 26 micrograms. ml-1.h, t1/2 beta = 16.5 h).
During the repeated doses study, 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 t1/2 beta of idebenone after the single and after
repeated dose studies, i.e., there was no evidence of accumulation. Although
idebenone did not appear to accumulate during this study, the coadministration
of anticonvulsants, often prescribed during mitochondrial encephalomyopathy,
can affect its pharmacokinetics