title: Effect of 3 Single-Dose Regimens of Opicapone on Levodopa Pharmacokinetics, Catechol-O-Methyltransferase Activity and Motor Response in Patients With Parkinson Disease.
abstract: This study determined the effects of single doses of opicapone (OPC), a novel third-generation catechol-O-methyltransferase (COMT) inhibitor, on levodopa and 3-O-methyl-levodopa (3-OMD) pharmacokinetics (PK), COMT activity and motor fluctuations in patients with Parkinson disease (PD). Subjects received, in a double-blind manner, 25, 50, and 100 mg OPC or placebo (PLC) in 4 separate treatment periods. The washout period between doses was at least 10 days. During each period, the OPC/PLC capsules were to be coadministered with the morning dose of 100/25 mg levodopa/carbidopa (LC) or levodopa/benserazide (LB) on day 3. In relation to PLC, levodopa exposure increased 3.7%, 16.4%, and 34.8% following 25, 50, or 100 mg OPC, respectively. Maximum S-COMT inhibition (Emax ) ranged from 67.8% (25 mg OPC) to 100% (100 mg OPC). Peak and extent of S-COMT inhibition were dose-dependent. Maximum decrease in the plasma 3-OMD was observed following administration of 100 mg OPC. Opicapone administered concomitantly with standard-release 100/25 mg LC or LB improved motor performance. Treatments were generally well tolerated and safe. It was concluded that OPC is a new COMT inhibitor that significantly decreased COMT activity and increased systemic exposure to levodopa in PD patients with motor fluctuations.
authors.affiliation: Department of Research and Development, BIAL - Portela & Cª - S.A., Coronado, Portugal.
authors.forename: José-Francisco
authors.initials: JF
authors.lastname: Rocha
authors.affiliation: Neurological Clinical Research Unit, Institute of Molecular Medicine, Lisbon, Portugal.
authors.forename: Joaquim J
authors.initials: JJ
authors.lastname: Ferreira
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
authors.forename: Amílcar
authors.initials: A
authors.lastname: Falcão
authors.affiliation: Department of Research and Development, BIAL - Portela & Cª - S.A., Coronado, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Santos
authors.affiliation: Department of Research and Development, BIAL - Portela & Cª - S.A., Coronado, Portugal.|Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pinto
authors.affiliation: Department of Research and Development, BIAL - Portela & Cª - S.A., Coronado, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Nunes
authors.affiliation: Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.|Health Sciences Department, University of Aveiro, Aveiro, Portugal, University Porto, Porto, Portugal.|MedInUP - Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal.
authors.forename: Luis
authors.initials: L
authors.lastname: Almeida
authors.affiliation: Department of Research and Development, BIAL - Portela & Cª - S.A., Coronado, Portugal.|Department of Pharmacology & Therapeutics, Faculty of Medicine, University of 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; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001545:Benserazide / Q000008:administration & dosage; D002230:Carbidopa / Q000008:administration & dosage; D002394:Catechol O-Methyltransferase / Q000187:drug effects / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010069:Oxadiazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy*
chemical_list: D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D004338:Drug Combinations; D010069:Oxadiazoles; C005177:benserazide, levodopa drug combination; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D001545:Benserazide; D002394:Catechol O-Methyltransferase; D002230:Carbidopa; C549349:opicapone
keywords: COMT inhibitor; Parkinson disease; levodopa; motor response; opicapone