Opicapone: a short lived and very long acting novel catechol-O-methyltransferase inhibitor following multiple dose administration in healthy subjects

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

Rocha, JF (Autor) Outra; Almeida, L (Autor) Outra; Falcao, A (Autor) Outra; Palma, PN (Autor) Outra; Loureiro, AI (Autor) Outra; Pinto, R (Autor) FMUP; Bonifacio, MJ (Autor) Outra; Wright, LC (Autor) Outra; Nunes, T (Autor) Outra; soares-da-silva, p (Autor) FMUP

Revista

Título: British Journal of Clinical Pharmacology

Vol. 76

Páginas: 763-775

ISSN: 0306-5251

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 56 Citações

Scopus - 58 Citações

Outras Informações

ID Authenticus: P-008-G0K

DOI: 10.1111/bcp.12081

Abstract (EN): AimsThe aim of this study was to assess the tolerability, pharmacokinetics and inhibitory effect on erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity following repeated doses of opicapone. MethodsThis randomized, placebo-controlled, double-blind study enrolled healthy male subjects who received either once daily placebo or opicapone 5, 10, 20 or 30mg for 8 days. ResultsOpicapone was well tolerated. Its systemic exposure increased in an approximately dose-proportional manner with an apparent terminal half-life of 1.0 to 1.4h. Sulphation was the main metabolic pathway. Opicapone metabolites recovered in urine accounted for less than 3% of the amount of opicapone administered suggesting that bile is likely the main route of excretion. Maximum S-COMT inhibition (E-max) ranged from 69.9% to 98.0% following the last dose of opicapone. The opicapone-induced S-COMT inhibition showed a half-life in excess of 100h, which was dose-independent and much longer than plasma drug exposure. Such a half-life translates into a putative underlying rate constant that is comparable with the estimated dissociation rate constant of the COMT-opicapone complex. ConclusionDespite its short elimination half-life, opicapone markedly and sustainably inhibited erythrocyte S-COMT activity making it suitable for a once daily regimen.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 13