Pharmacokinetics of opicapone, a third-generation COMT inhibitor, after single and multiple oral administration: A comparative study in the rat.
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.
['Gonçalves|Daniela|D|', 'Alves|Gilberto|G|', 'Fortuna|Ana|A|', 'Soares-da-Silva|Patrício|P|', 'Falcão|Amílcar|A|']
D000284:Administration, Oral D000818:Animals D019540:Area Under Curve D065098:Catechol O-Methyltransferase Inhibitors D004334:Drug Administration Schedule D065569:Gastrointestinal Absorption D006207:Half-Life D008297:Male D008657:Metabolic Clearance Rate D008954:Models, Biological D010069:Oxadiazoles D017208:Rats, Wistar D018570:Risk Assessment
Pharmacokinetics Opicapone Rat Catechol-O-methyltransferase inhibitor