CRITICAL REVIEW AND INVITED COMMENTARY
Pharmacokinetics and drug interactions of eslicarbazepine acetate
Article first published online: 21 MAY 2012
Wiley Periodicals, Inc. © 2012 International League Against Epilepsy
Volume 53, Issue 6, pages 935–946, June 2012
How to Cite
Bialer, M. and Soares-da-Silva, P. (2012), Pharmacokinetics and drug interactions of eslicarbazepine acetate. Epilepsia, 53: 935–946. doi: 10.1111/j.1528-1167.2012.03519.x
- Issue published online: 1 JUN 2012
- Article first published online: 21 MAY 2012
- Accepted March 29, 2012; Early View publication March 21, 2012.
- Antiepileptic drugs;
- Eslicarbazepine acetate;
- Drug interactions
Eslicarbazepine acetate (ESL) is a novel once-daily antiepileptic drug (AED) approved in Europe since 2009 that was found to be efficacious and well tolerated in a phase III clinical program in adult patients with partial onset seizures previously not controlled with treatment with one to three AEDs, including carbamazepine (CBZ). ESL shares with CBZ and oxcarbazepine (OXC) the dibenzazepine nucleus bearing the 5-carboxamide substitute, but is structurally different at the 10,11 position. This molecular variation results in differences in metabolism, preventing the formation of toxic epoxide metabolites such as carbamazepine-10,11-epoxide. Unlike OXC, which is metabolized to both eslicarbazepine and (R)-licarbazepine, ESL is extensively converted to eslicarbazepine. The systemic exposure to eslicarbazepine after ESL oral administration is approximately 94% of the parent dose, with minimal exposure to (R)-licarbazepine and OXC. After ESL oral administration, the effective half-life (t1/2,eff) of eslicarbazepine was 20–24 h, which is approximately two times longer than its terminal half-life (t1/2). At clinically relevant doses (400–1,600 mg/day) ESL has linear pharmacokinetics (PK) with no effects of gender or moderate liver impairment. However, because eslicarbazepine is eliminated primarily (66%) by renal excretion, dose adjustment is recommended for patients with renal impairment. Eslicarbazepine clearance is induced by phenobarbital, phenytoin, and CBZ and it dose-dependently decreases plasma exposure of oral contraceptive and simvastatin.