PURPOSE: Opicapone (OPC) is a novel catechol-O-methyltransferase (COMT) 
inhibitor to be used as adjunctive therapy in levodopa-treated patients with 
Parkinson's disease. The purpose of this study was to evaluate the effect of 
moderate liver impairment on the pharmacokinetics (PK) and pharmacodynamics (PD; 
effect on COMT activity) of OPC.
METHODS: An open-label, parallel-group study in patients (n = 8) with moderate 
liver impairment (Child-Pugh category B, score of 7 to 9) and matched healthy 
subjects (n = 8, control) with normal liver function. All subjects received a 
single 50-mg oral dose of OPC, with plasma and urine concentrations of opicapone 
and its metabolites measured up to 72 h post-dose, including soluble COMT 
(S-COMT) activity. A one-way analysis of variance (ANOVA) was used to compare 
the main PK and PD parameters between groups. Point estimates (PE) of geometric 
mean ratios (GMR) and corresponding 90 % confidence intervals (90%CI) for the 
ratio hepatic/control subjects of each parameter were calculated and compared 
with the reference interval (80-125 %).
RESULTS: Exposure to opicapone (AUC and Cmax) increased significantly in 
patients with moderate hepatic impairment (PE [90%CI]: AUC0-∞, 184 % 
[135-250 %]; Cmax, 189 % [144-249 %]). Although apparent total clearance (CL/F) 
of opicapone was decreased by ∼35 %, similar elimination half-life and 
unbound/bound fractions of opicapone were observed between the two groups. Both 
rate and extent of exposure to BIA 9-1103 were higher in the hepatically 
impaired group, but not statistically significant compared with the control 
group. Similar to the parent (opicapone), the observed increase in exposure to 
BIA 9-1106 was statistically significant in the hepatically impaired group over 
the control group. BIA 9-1106 was the only metabolite detected in urine and its 
urine PK parameters were in accordance with plasma data. Maximum S-COMT 
inhibition (Emax) occurred earlier for the hepatically impaired group with 
values of 100 % and 91.2 % for the hepatically impaired and control groups 
respectively. Both Emax and AUEC for the hepatically impaired group reached 
statistical significance over the control group. OPC was well tolerated in both 
hepatically impaired and control groups.
CONCLUSION: The bioavailability of an orally administered single dose of 50 mg 
OPC was significantly higher in patients with moderate chronic hepatic 
impairment, perhaps by a reduced first-pass effect. As the tolerability profile 
of OPC was favourable under the conditions of this study and its exposure is 
completely purged from systemic circulation before the subsequent dose 
administration, no OPC dose adjustment is needed in patients with mild to 
moderate chronic hepatic impairment. However, as OPC is under clinical 
development for use as adjunctive therapy in levodopa-treated patients with 
Parkinson's disease, an adjustment of levodopa and/or OPC regimens in patients 
should be carefully considered based on a potentially enhanced levodopa 
dopaminergic response and the associated tolerability.