title: Opicapone pharmacokinetics and pharmacodynamics comparison between healthy Japanese and matched white subjects.
abstract: Opicapone (OPC) is a novel third-generation catechol-O-methyltransferase (COMT) inhibitor. This randomized, double-blind, parallel, placebo-controlled and multiple ascending dose study in 3 sequential groups of up to 38 (19 Japanese plus 19 white subjects) aimed to compare the pharmacokinetics (PK) and pharmacodynamics (PD; COMT activity) of opicapone between healthy Japanese and matched white subjects. Enrolled subjects received a once-daily morning administration of OPC (5, 25, or 50 mg) or placebo for 10 days, with plasma and urine concentrations of opicapone and its metabolites measured up to 144 hours postdose, including S-COMT activity. Geometric mean ratios (GMRs) and confidence intervals (95%CIs) for the main PK and PD parameters of OPC were evaluated between populations. Both the PK and PD of OPC were similar in the Japanese and white populations. Overall, only minimal differences were noted between the 2 populations, which were not deemed to be statistically significant. When both populations were separated based on their COMT genotype, the observed PK and PD differences were also negligible. In conclusion, the PK and PD profiles of OPC were similar in the Japanese and white populations. Thus, ethnicity and COMT polymorphisms had no significant impact on the OPC PK and PD in the conditions of the study.
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, Coimbra, Portugal.
authors.forename: Amílcar
authors.initials: A
authors.lastname: Falcão
authors.affiliation: Department of Research & Development, BIAL - Portela & Cª - S.A., Mamede do Coronado, Portugal.
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Rocha
authors.affiliation: Department of Research & Development, BIAL - Portela & Cª - S.A., Mamede do Coronado, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Santos
authors.affiliation: Department of Research & Development, BIAL - Portela & Cª - S.A., Mamede do Coronado, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Nunes
authors.affiliation: Department of Research & Development, BIAL - Portela & Cª - S.A., Mamede do Coronado, Portugal.|Department of Pharmacology & Therapeutics, Faculty of Medicine, University Porto, Porto, Portugal.|MedInUP - Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal.
authors.forename: Patrício
authors.initials: P
authors.lastname: Soares-da-Silva
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D002394:Catechol O-Methyltransferase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010069:Oxadiazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D011110:Polymorphism, Genetic; D044465:White People; D055815:Young Adult
chemical_list: D065098:Catechol O-Methyltransferase Inhibitors; D010069:Oxadiazoles; D002394:Catechol O-Methyltransferase; C549349:opicapone
keywords: COMT inhibitors; Japanese; opicapone; pharmacokinetics; polymorphisms