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.
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.
Daniela
D
Gonçalves
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. Electronic address: gilberto@fcsaude.ubi.pt.
Gilberto
G
Alves
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.
Ana
A
Fortuna
Department of Research and Development, BIAL - Portela & Cª S.A., Av. da Siderurgia Nacional, 4745-457 S. Mamede do Coronado, Portugal; MedInUP - Center for Drug Discovery and Innovative Medicines, University Porto, Porto, Portugal.
Patrício
P
Soares-da-Silva
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.
Amílcar
A
Falcão
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D065098:Catechol O-Methyltransferase Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D004334:Drug Administration Schedule; D065569:Gastrointestinal Absorption; D006207:Half-Life; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010069:Oxadiazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D017208:Rats, Wistar; D018570:Risk Assessment
D065098:Catechol O-Methyltransferase Inhibitors; D010069:Oxadiazoles; C549349:opicapone
Catechol-O-methyltransferase inhibitor; Opicapone; Pharmacokinetics; Rat