Abstracts

The objective was to determine the pharmacokinetics of eslicarbazepine acetate following single and repeated doses. Integrated pharmacokinetic results of three double-blind, randomised, placebo-controlled trials. Oral single doses of eslicarbazepine acetate ranging from 20 mg to 2400 mg, and 8-day oral repeated doses ranging from 400 mg to 2400 mg daily were administered to healthy young male subjects (6 subjects per dose). Previous human studies in which a chiral method has been used in the assay of plasma drug concentrations showed that eslicarbazepine acetate is rapidly and extensively transformed into the active metabolite eslicarbazepine (also known as S-licarbazepine), which represents more than 95% of systemic drug exposure following oral administration of eslicarbazepine acetate. When a non-chiral method is used, which was the case of the current trials, the assay is not able to distinguish between eslicarbazepine and its R-enantiomer (R-licarbazepine), a minor metabolite, and the mixture is reported as BIA 2-005. Eslicarbazepine acetate was extensively metabolized to BIA 2-005. The summary of the main BIA 2-005 pharmacokinetic parameters following repeated (8-day treatment) doses can be found in Tables I. Both the rate and the extent of systemic exposure to BIA 2-005 increased in an approximately dose-proportional manner following repeated administration. The mean observed accumulation (R[sub]O[/sub]) was 1.4, 1.7, 1.7, 1.5 and 2.1 after once-daily dosing (q.d.) with the 400 mg, 800 mg, 1200 mg, 1800 mg and 2400 mg doses, respectively. Steady-state plasma BIA 2-005 concentrations were attained at 4 to 5 days of once-daily dosing, consistent with an effective elimination half-life (t[sub]1/2[/sub]) in the order of 20 h to 24 h. Renal clearance of BIA 2-005 appeared to be constant over the dose range studied. Eslicarbazepine acetate appeared to be rapidly and extensively metabolized to BIA 2-005 following single and repeated administration to healthy young subjects. Moreover, the dose-proportionality for BIA 2-005 (following single and repeated doses) is in accordance with the concept of linearity regarding its pharmacokinetic behaviour (rate and extent of systemic exposure).[table1]