Abstracts

Rationale: Anti-epileptic drugs can be used by patients with liver impairment. The objective of this study was to evaluate the effect of moderate liver impairment on the pharmacokinetics of eslicarbazepine acetate (BIA 2-093, ESL), a novel anti-epileptic drug in clinical development.Methods: The pharmacokinetics of ESL following a 8-day 800 mg once-daily administration was characterized in patients with moderate liver impairment (n=8) and in subjects with normal liver function (n=8, control group).Results: ESL was rapidly and extensively metabolized by first-pass metabolism to its main active metabolite, eslicarbazepine (S-licarbazepine). In the hepatic impairment group, there were more subjects with measurable plasma concentrations of parent drug (ESL) than in the control group, suggesting that first-pass metabolism was slightly decreased by liver impairment. However, ESL plasma concentrations remained very low, representing only about 0.01% of total systemic exposure. No differences in eslicarbazepine pharmacokinetic parameters were found between the hepatic impaired and control groups. Eslicarbazepine total body clearance and renal clearance (CL/F and CLR) were respectively 2.15 L/h and 1.33 L/h in the impairment group and 2.17 L/h and 1.39 L/h in the control group. No difference on the rate or extent of eslicarbazepine-glucuronide formation was found. Eslicarbazepine and eslicarbazepine-glucuronide urine excretions were similar in liver impaired and control subjects. No pharmacokinetic differences were found between the minor metabolites R-licarbazepine, oxcarbazepine and their respective glucuronides.Conclusions: The pharmacokinetics of eslicarbazepine acetate was not affected by moderate hepatic impairment. Therefore, patients with mild to moderate liver impairment treated with eslicarbazepine acetate do not need dose adjustment.