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

• Type: Article in International Scientific Journal
• Date: 2013

Authors

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

Journal

Title: British Journal of Clinical Pharmacology

Vol. 76

Pages: 763-775

ISSN: 0306-5251

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 56 Citations

Scopus - 58 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13