Pharmacokinetics of eslicarbazepine acetate at steady-state in adults with partial-onset seizures

SummaryObjectiveTo evaluate the pharmacokinetics of eslicarbazepine acetate (ESL) at steady-state in adults with partial-onset seizures who have taken ESL for at least 1 year with one or two concomitant antiepileptic drugs (AEDs).MethodsBlood samples for the pharmacokinetic assessment were taken at pre-dose, and 1, 2, 3, 4, 6, 8, 12 and 24 h post-dose at steady-state in 51 patients stabilised on chronic (beyond 1 year) treatment with ESL 400 mg (n = 7), 800 mg (n = 26) or 1200 mg (n = 18) once-daily. Most patients (n = 29, 56.9%) were receiving 2 concomitant AEDs, and most frequent co-medications were carbamazepine (n = 34, 66.7%) and valproic acid (n = 19, 37.3%). Plasma concentrations of ESL and its metabolites eslicarbazepine, R-licarbazepine and oxcarbazepine (OXC) were determined by a validated chiral method using liquid chromatography coupled to mass spectrometry.ResultsSimilarly to earlier findings in healthy subjects, plasma ESL concentrations were consistently below the lower limit of quantification (50 ng/mL). The major compound in plasma was the active metabolite eslicarbazepine, which reached maximum concentrations (Cmax) 2 h post-dose; thereafter, its plasma concentrations declined with a mean apparent half-life of 13, 14, and 20 h in patients receiving ESL doses of 400, 800, and 1200 mg once daily, respectively. Eslicarbazepine Cmax were 9.7, 15.5 and 23.0 μg/mL, and areas under the plasma concentration⿿time curve over the dosing interval (AUC0⿿24) were 132.5, 205.4 and 336.1 μg h/mL in patients receiving ESL doses of 400, 800 and 1200 mg once-daily, respectively. Eslicarbazepine main pharmacokinetic parameters (Cmax and AUC0⿿24) were dose-proportional. R-licarbazepine and OXC were minor metabolites.ConclusionsFollowing once-daily oral administration of ESL 400 mg, 800 mg and 1200 mg to epilepsy patients treated concomitantly with one or two other AEDs, ESL was rapidly converted to eslicarbazepine, which was the primary active compound found in plasma. Systemic exposure to eslicarbazepine was dose-proportional.