title: Effect of opicapone multiple-dose regimens on levodopa pharmacokinetics.
abstract: To compare the levodopa/carbidopa (LC) and levodopa/benserazide (LB) pharmacokinetic profiles following repeated doses of opicapone (OPC) administered apart from levodopa.
  
  
  
  Two randomized, double blind, sex-balanced, placebo-controlled studies in four groups of 12 or 18 healthy subjects each. In each group, enrolled subjects received a once-daily morning (5, 15 and 30 mg) or evening (5, 15 and 50 mg) administration of OPC or placebo for up to 28 days. On the morning of Day 11, 12 h after the OPC or placebo evening dose, or the morning of Day 21, 1 h after the OPC or placebo dose, a single dose of immediate-release 100/25 mg LC was administered. Similarly, on Day 18 morning, 12 h after the OPC or placebo evening dose, or Day 28 morning, 1 h after the OPC or placebo dose, a single dose of immediate-release 100/25 mg LB was administered.
  
  
  
  All OPC treatments, in relation to the placebo group, presented a higher extent of exposure (AUC) to levodopa following either LC or LB doses. A relevant but not dose-dependent increase in the levodopa AUC occurred with all OPC dose groups in relation to placebo. All active treatments significantly inhibited both peak (Emax) and extent (AUEC) of the catechol-O-methyltransferase activity in relation to placebo. The tolerability profile was favourable.
  
  
  
  Opicapone, as once-daily oral evening regimen and/or 1 h apart from levodopa therapy, increases the bioavailability of levodopa associated with its pronounced, long-lasting and sustained catechol-O-methyltransferase inhibition. The tolerability profile was favourable and similar between OPC and placebo.
authors.affiliation: Dept. Research & Development, BIAL - Portela & Cª - S.A., 4745-457, S. Mamede do Coronado, Portugal.
authors.forename: José-Francisco
authors.initials: JF
authors.lastname: Rocha
authors.affiliation: Algorithme Pharma Inc., Quebec, Canada.
authors.forename: Éric
authors.initials: É
authors.lastname: Sicard
authors.affiliation: Biotrial, Rennes, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fauchoux
authors.affiliation: Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
authors.forename: Amílcar
authors.initials: A
authors.lastname: Falcão
authors.affiliation: Dept. Research & Development, BIAL - Portela & Cª - S.A., 4745-457, S. Mamede do Coronado, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Santos
authors.affiliation: Dept. Research & Development, BIAL - Portela & Cª - S.A., 4745-457, S. Mamede do Coronado, Portugal.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Loureiro
authors.affiliation: Dept. Research & Development, BIAL - Portela & Cª - S.A., 4745-457, S. Mamede do Coronado, Portugal.|Dept. Pharmacology & Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pinto
authors.affiliation: Dept. Research & Development, BIAL - Portela & Cª - S.A., 4745-457, S. Mamede do Coronado, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Bonifácio
authors.affiliation: Dept. Research & Development, BIAL - Portela & Cª - S.A., 4745-457, S. Mamede do Coronado, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Nunes
authors.affiliation: Dept. 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: Luís
authors.initials: L
authors.lastname: Almeida
authors.affiliation: Dept. Research & Development, BIAL - Portela & Cª - S.A., 4745-457, S. Mamede do Coronado, Portugal.|Dept. 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; D000978:Antiparkinson Agents / Q000493:pharmacokinetics; D001545:Benserazide / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D002230:Carbidopa / Q000009:adverse effects / Q000494:pharmacology; D065098:Catechol O-Methyltransferase Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010069:Oxadiazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D004338:Drug Combinations; D010069:Oxadiazoles; C005177:benserazide, levodopa drug combination; D007980:Levodopa; D001545:Benserazide; D002230:Carbidopa; C549349:opicapone
keywords: benserazide; carbidopa; catechol-O-methyltransferase inhibitors; levodopa; opicapone; pharmacokinetics