Abstracts

Rationale: The aim of this pharmacokinetic/pharmacodynamic (PK/PD) analysis was to model the relationship between the exposure to eslicarbazepine (the main active metabolite of eslicarbazepine acetate, ESL) and the antiepileptic efficacy of ESL in adult patients with partial-onset seizures refractory to treatment with 1-3 concomitant antiepileptic drugs. Methods: Data from patients enrolled in three double-blind, placebo-controlled, phase 3 clinical studies were used in this analysis. Patients were treated with ESL once-daily doses of 400, 800 and 1200 mg. Seizures were recorded on diaries at baseline and during the treatment phases. Population PK/PD modelling was performed using NONMEM. Results: Efficacy variables derived from the seizure frequency standardised for 4 weeks were best fitted by a combination of a baseline, a placebo effect and an effect of ESL described by an Emax function. The antiepileptic effect of ESL, as assessed by a decrease in seizure frequency, increased with the increase of ESL dose. The probability of being a responder (at least a 50% reduction in seizure frequency) or seizure-free increased as a function of eslicarbazepine concentrations. Conclusions: Overall, the results of this population PK/PD analysis demonstrated a continuous relationship, with moderate inter-subject variability, between antiepileptic efficacy and eslicarbazepine concentrations, that were not affected by concomitant AEDs. Support: BIAL - Portela & Co, SA.