Pisano P, Durand A, Autret E, Desnuelle C, Pinsard N, Serratrice G, Legout V, Joubert M, Blin O
Pharmacologie Médicale et Clinique, CHU Timone Bt F-13385 Marseille, France.
Eur J Clin Pharmacol. 1996;51(2):167-9. doi: 10.1007/s002280050179.
The pharmacokinetics and tolerance of idebenone after single or repeated doses have been studied in young patients with mitochondrial encephalomyopathy.
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.
在患有线粒体脑肌病的年轻患者中研究艾地苯醌单次或重复给药后的药代动力学和耐受性。
未观察到明显的不良反应。7名患者中有3名患者在服用艾地苯醌后出现整体兴奋和觉醒改善。测定了艾地苯醌及其主要代谢物的血浆浓度，并估算了单次和重复给药后艾地苯醌的药代动力学参数。在单次给药研究中，艾地苯醌及其主要代谢物的平均血浆浓度和平均药代动力学参数与已发表的结果相当（Cmax = 452.2 ng.ml-1，tmax = 2.3 h，AUC = 26 μg.ml-1.h，t1/2β = 16.5 h）。在重复给药研究中，第2天（47 ng.ml-1）和第5天（70.6 ng.ml-1）艾地苯醌的平均残留血浆浓度之间以及单次和重复给药研究后艾地苯醌的平均t1/2β之间均未发现显著差异，即没有蓄积证据。尽管在本研究中艾地苯醌似乎没有蓄积，但线粒体脑肌病患者常开具的抗惊厥药的联合使用可能会影响其药代动力学。
