Abstracts

Rationale: Anti-epileptic drugs are often used in combination. This study aimed to assess the potential for pharmacokinetic interaction between eslicarbazepine acetate (ESL) 1200 mg and lamotrigine (LAM) 150 mg following repeated administration in healthy subjects. Methods: Multiple-dose, open-label, one-sequence, parallel-group design study in 32 healthy male volunteers (16 per group) aiming to evaluate the effect of ESL 1200 mg once-daily (QD) repeated administration on the lamotrigine (LAM) pharmacokinetics (A) and effect of LAM 150 mg QD repeated administration on the ESL pharmacokinetics (B). The bioequivalence approach was used for assessing the drug-drug pharmacokinetic interactions.Results: ESL was rapidly and extensively metabolized to eslicarbazepine, the main active metabolite. Geometric mean ratios (end:start of treatment) and 90% confidence intervals (90% CI) were calculated for Cmax and AUC of eslicarbazepine and LAM. The results were as follows: (A) Following ESL 1200 mg QD, mean ratio (90% CI) was 0.88 (0.82, 0.94) for LAM Cmax and 0.86 (0.81, 0.92) for LAM AUC. (B) Following LAM 150 mg QD, mean ratio (90% CI) was 0.95 for eslicarbazepine Cmax (0.87, 1.02) and 0.96 (0.91, 1.02) for eslicarbazepine AUC. The 90% CI of the geometric mean ratios for Cmax and AUC fall within the pre-specified bioequivalence range (0.80, 1.25) both for eslicarbazepine and LAM. Therefore, the bioavailability of LAM at steady-state was essentially bioequivalent to LAM in the presence of ESL, and that the bioavailability of eslicarbazepine at steady-state was essentially bioequivalent to eslicarbazepine in the presence of LAM.Conclusions: No pharmacokinetic interaction between ESL 1200 mg QD and lamotrigine 150 mg QD was observed following concomitant repeated administration in healthy subjects.