Pharmacokinetics and drug interactions of eslicarbazepine acetate.
Article Details
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Bialer M, Soares-da-Silva P
Pharmacokinetics and drug interactions of eslicarbazepine acetate.
Epilepsia. 2012 Jun;53(6):935-46. doi: 10.1111/j.1528-1167.2012.03519.x. Epub 2012 May 21.
- PubMed ID
- 22612290 [ View in PubMed]
- Abstract
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 (t(1/2,eff) ) of eslicarbazepine was 20-24 h, which is approximately two times longer than its terminal half-life (t(1/2)). 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.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Eslicarbazepine Cytochrome P450 2C19 Protein Humans UnknownInhibitorDetails Eslicarbazepine acetate Cytochrome P450 2C19 Protein Humans NoInhibitorDetails Eslicarbazepine acetate Cytochrome P450 3A4 Protein Humans NoInducerDetails - Drug Reactions
Reaction Details Details Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareEslicarbazepineCarbamazepine The risk or severity of adverse effects can be increased when Carbamazepine is combined with Eslicarbazepine. EslicarbazepinePhenytoin The serum concentration of Eslicarbazepine can be decreased when it is combined with Phenytoin. EslicarbazepineMephenytoin The serum concentration of Eslicarbazepine can be decreased when it is combined with Mephenytoin. EslicarbazepinePrimidone The serum concentration of Eslicarbazepine can be decreased when it is combined with Primidone. EslicarbazepinePhenobarbital The serum concentration of Eslicarbazepine can be decreased when it is combined with Phenobarbital.
