AIMS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: Despite its short elimination half-life, opicapone markedly and 
sustainably inhibited erythrocyte S-COMT activity making it suitable for a once 
daily regimen.