Abstracts

Rationale: Eslicarbazepine acetate (ESL), a novel antiepileptic drug (AED), has been studied as adjunctive therapy in patients with refractory partial seizures. The purpose of this population pharmacokinetic (PK) analysis was to investigate the possible effect of ESL on the PK of nine co-administered AEDs (valproate, phenytoin, topiramate, lamotrigine, carbamazepine, gabapentin, phenobarbital, clobazam and levetiracetam) in adult patients with refractory partial epilepsy. Methods: The study population consisted of refractory patients (n≥30 patients per AED) who participated in 3 ESL add-on Phase 3 studies. Population PK analysis was performed using NONMEM. Since it was not possible to fit a complete PK model to the data, only one parameter for each AED was estimated: the apparent clearance (CL/F). Results: The estimated CL/F for the nine AEDs agreed with values found in the literature using a similar approach. The known interactions between these marketed AEDs were also apparent within the data from this integrated analysis. Multiple dose administration of ESL 400 mg to 1200 mg once-daily did not affect the CL/F of clobazam (n=61), gabapentin (n=31), phenytoin (n=81), phenobarbital (n=93), levetiracetam (n=92) and valproate (n=209) and only slightly increased the clearance of carbamazepine (n=526), lamotrigine (n=203) and topiramate (n=118). Conclusions: The effects of ESL on CL/F of those concomitant AEDs assessed appears not to be clinically relevant. ESL can be co-administered with these AEDs without concern for clinically significant changes in their PK profile. Support: BIAL - Portela & Co, SA.