Gonçalves Daniela, Alves Gilberto, Fortuna Ana, Soares-da-Silva Patrício, Falcão Amílcar
Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.
Toxicol Appl Pharmacol. 2017 May 15;323:9-15. doi: 10.1016/j.taap.2017.03.013. Epub 2017 Mar 16.
Opicapone is a novel potent, reversible and purely peripheral catechol-O-methyltransferase inhibitor that has been developed to be used as an adjunct to levodopa/aromatic L-amino acid decarboxylase inhibitor therapy for Parkinson's disease. Thus, this study aimed to compare the plasma pharmacokinetics of opicapone and its active metabolite (BIA 9-1079) after the administration of single and multiple oral doses to rats. Wistar rats (n=8 per group) were orally treated with single (30, 60 or 90mg/kg) or multiple (30mg/kg once-daily for seven consecutive days) oral doses of opicapone. Blood samples were collected up to 24h post-dosing through a cannula introduced in the tail vein of rats. After quantifying opicapone and BIA 9-1079 in plasma, a non-compartmental pharmacokinetic analysis was performed. Opicapone was quickly absorbed (time to reach the maximum plasma concentration≤2h) in both dosage regimens and the extent of systemic exposure to opicapone increased approximately in a dose-proportional manner after single-dosing within the studied dose range (30-90mg/kg). Opicapone and BIA 9-1079 showed a relatively short plasma elimination half-life (1.58-4.50h) and a small systemic accumulation after multiple-dosing. Hence, no pharmacokinetic concerns are expected when opicapone is administered with a once-daily dosing regimen.
奥匹卡朋是一种新型的强效、可逆且纯粹的外周儿茶酚-O-甲基转移酶抑制剂，已被开发用作左旋多巴/芳香族L-氨基酸脱羧酶抑制剂治疗帕金森病的辅助药物。因此，本研究旨在比较大鼠单次和多次口服给药后奥匹卡朋及其活性代谢物（BIA 9-1079）的血浆药代动力学。将Wistar大鼠（每组n = 8）口服给予单次（30、60或90mg/kg）或多次（30mg/kg，连续7天每日一次）口服剂量的奥匹卡朋。通过插入大鼠尾静脉的套管在给药后24小时内采集血样。在对血浆中的奥匹卡朋和BIA 9-1079进行定量后，进行非房室药代动力学分析。在两种给药方案中，奥匹卡朋均迅速吸收（达到最大血浆浓度的时间≤2小时），并且在研究剂量范围内（30-90mg/kg）单次给药后，奥匹卡朋的全身暴露程度大致呈剂量比例增加。奥匹卡朋和BIA 9-1079的血浆消除半衰期相对较短（1.58-4.50小时），多次给药后全身蓄积较小。因此，当奥匹卡朋采用每日一次的给药方案给药时，预计不存在药代动力学方面的问题。
