caa a22 4500 477056768 CHVBK 20180405111348.0 cr unu---uuuuu 170330e19961001xx s 000 0 eng 10.1007/s002280050179 doi (NATIONALLICENCE)springer-10.1007/s002280050179 Plasma concentrations and pharmacokinetics of idebenone and its metabolites following single and repeated doses in young patients with mitochondrial encephalomyopathy [Elektronische Daten] [P. Pisano, A. Durand, E. Autret, C. Desnuelle, N. Pinsard, G. Serratrice, V. Legout, M. Joubert, O. Blin] Objective: The pharmacokinetics and tolerance of idebenone after single or repeated doses have been studied in young patients with mitochondrial encephalomyopathy. 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 μg ⋅ ml−1 ⋅ h, t1/2β = 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 t1/2β 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. Springer-Verlag Berlin Heidelberg, 1996 Key words Idebenone nationallicence mitochondrial encephalomyopathy nationallicence young patients nationallicence pharmacokinetics nationallicence Pisano P. Laboratoire de Pharmacocinétique et Toxicocinétique, CHU Timone, 254 rue St Pierre, F-133855 Marseille Cedex 5, France, FR aut Durand A. Laboratoire de Pharmacocinétique et Toxicocinétique, CHU Timone, 254 rue St Pierre, F-133855 Marseille Cedex 5, France, FR aut Autret E. Laboratoire de Pharmacologie, Hôpital Bretonneau, F-37044 Tours, France, FR aut Desnuelle C. Service de Neurologie, Laboratoire de Neurobiologie Cellulaire, Hôpital Pasteur, BP 69, F-06002 Nice, France, FR aut Pinsard N. Service de Neurologie Pédiatrique, CHU Timone Enfants, F-13385 Marseille Cedex 5, France, FR aut Serratrice G. Clinique des Maladies du Système Nerveux et de l'Appareil Locomoteur, CHU Timone Adultes, F-13385 Marseille Cedex 5, France, FR aut Legout V. Laboratoires Takeda, 15 Quai de Dion Bouton, F-92816 Puteaux Cedex, France, FR aut Joubert M. Laboratoires Takeda, 15 Quai de Dion Bouton, F-92816 Puteaux Cedex, France, FR aut Blin O. Pharmacologie Médicale et Clinique and Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques, CHU Timone Bt F-13385 Marseille Cedex 5, France, FR aut https://doi.org/10.1007/s002280050179 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050179 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pisano P. Laboratoire de Pharmacocinétique et Toxicocinétique, CHU Timone, 254 rue St Pierre, F-133855 Marseille Cedex 5, France, FR aut NATIONALLICENCE 700 1- Durand A. Laboratoire de Pharmacocinétique et Toxicocinétique, CHU Timone, 254 rue St Pierre, F-133855 Marseille Cedex 5, France, FR aut NATIONALLICENCE 700 1- Autret E. Laboratoire de Pharmacologie, Hôpital Bretonneau, F-37044 Tours, France, FR aut NATIONALLICENCE 700 1- Desnuelle C. Service de Neurologie, Laboratoire de Neurobiologie Cellulaire, Hôpital Pasteur, BP 69, F-06002 Nice, France, FR aut NATIONALLICENCE 700 1- Pinsard N. Service de Neurologie Pédiatrique, CHU Timone Enfants, F-13385 Marseille Cedex 5, France, FR aut NATIONALLICENCE 700 1- Serratrice G. Clinique des Maladies du Système Nerveux et de l'Appareil Locomoteur, CHU Timone Adultes, F-13385 Marseille Cedex 5, France, FR aut NATIONALLICENCE 700 1- Legout V. Laboratoires Takeda, 15 Quai de Dion Bouton, F-92816 Puteaux Cedex, France, FR aut NATIONALLICENCE 700 1- Joubert M. Laboratoires Takeda, 15 Quai de Dion Bouton, F-92816 Puteaux Cedex, France, FR aut NATIONALLICENCE 700 1- Blin O. Pharmacologie Médicale et Clinique and Centre de Pharmacologie Clinique et d'Evaluations Thérapeutiques, CHU Timone Bt F-13385 Marseille Cedex 5, France, FR aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer