The 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. This randomized, placebo-controlled, double-blind study enrolled healthy male subjects who received either once daily placebo or opicapone 5, 10, 20 or 30 mg for 8 days. Opicapone was well tolerated. Its systemic exposure increased in an approximately dose-proportional manner with an apparent terminal half-life of 1.0 to 1.4 h. 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 (Emax ) 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 100 h, 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. Despite its short elimination half-life, opicapone markedly and sustainably inhibited erythrocyte S-COMT activity making it suitable for a once daily regimen.
The 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 . This randomized , placebo - controlled , double - blind study enrolled healthy male subjects who received either once daily placebo or opicapone 5 , 10 , 20 or 30 mg for 8 days . Opicapone was well tolerated . Its systemic exposure increased in an approximately dose - proportional manner with an apparent terminal half - life of 1.0 to 1.4 h. 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 ( Emax ) 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 100 h , 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 . Despite its short elimination half - life , opicapone markedly and sustainably inhibited erythrocyte S - COMT activity making it suitable for a once daily regimen .
What enzyme is inhibied by Opicapone?
What enzyme is inhibied by Opicapone ?
catechol-O-methyltransferase
catechol-O-methyltransferase