主催: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
会議名: WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
開催地: Kyoto
開催日: 2018/07/01 - 2018/07/06
Objectives: Evaluation of the pharmacokinetics of opicapone in the Wistar rat and the Cynomolgus monkey.
Methods: Opicapone disposition was evaluated in the Wistar rat and Cynomolgus monkey after intravenous (1 mg/kg) and oral administration (10 mg/kg) of [14C]-opicapone.
Results: Five to seven days after administration of [14C]-opicapone, more than 89.0% and more than 68% of opicapone related radioactivity had been excreted in rats and in monkeys, respectively. The radioactivity peaked in plasma at 4 and 0.25 h post-dosing in rats and monkeys, respectively, followed by a quick decline and a very slow terminal phase. Opicapone related radioactivity was mainly recovered in feces with very low levels (less than 10%) excreted in urine in both species, rat and monkey. Whole body autoradiography studies in rat following single oral administration of [14C]-opicapone (10 mg/kg), indicate that radioactivity was rapidly absorbed and distributed throughout the body. No quantifiable levels of radioactivity was detected in brain up to 24h. The high tissue to blood ratio of total radioactivity observed in liver and kidney at 48h post-dosing suggests a slower elimination of opicapone related radioactivity from these tissues. Following oral administration of 1000 mg/kg opicapone, opicapone-3-O-sulfate, opicapone-3-O-glucuronide and the N-oxide reduced form of opicapone were quantified in rat and monkey, with the exception of the N-oxide reduced form for which the AUC0-t was higher in monkeys, the exposure to opicapone and quantified metabolites were higher in rat. The relative abundancies of opicapone metabolites were diferente, however the metabolic profile was qualitatively similar in rat and monkey,
Conclusions: Opicapone was found to be rapidly absorbed and primarily excreted via feces in the Cynomolgus monkey and the Wistar rat. Although differences in relative abundances were observed, the metabolic profile of opicapone was qualitatively similar in rat and in monkey.
