Pharmacokinetic evaluation of idebenone.

摘要: Importance of the field Idebenone is a synthetic short chain benzoquinone that acts as an electron carrier in mitochondrial transport chain, thereby, facilitating production ATP. In addition, idebenone antioxidant and can inhibit lipid peroxidation may protect cell membranes mitochondria from oxidative damage. High dose (Catena(®)) approved Canada for symptomatic treatment Friedreich's ataxia currently under clinical investigation use number neuromuscular diseases. Areas covered this review This summarizes pharmacology, pharmacokinetic efficacy/safety data its metabolites provides update trials completed progress. What reader will gain Following oral administration, rapidly metabolized via shortening by CYP isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6 CYP3A4) to yield QS10, QS8, QS6 QS4. these concomitantly undergo conjugation glucuronidation sulfatation conjugated moieties represented idebenone-C, QS10-C, QS8-C, QS6-C QS4-C. Previous reports literature were only able quantify plasma concentrations measured together with conjugates. More recently, highly sensitive specific liquid chromatography method tandem mass spectrometric methods have been developed, allowing quantification parent molecule main metabolite separately. Take home message After absorption, first pass metabolism shows dose-proportional pharmacokinetics healthy subjects daily doses up 2250 mg. The recent development advanced analytical techniques allows detection unconjugated consequently opens possibility evaluation pharmacokinetic/pharmacodynamic relationships which be helpful further understand therapeutic potential idebenone. studies, was safe well tolerated at mg/day.