Pharmacokinetics and drug interactions of eslicarbazepine acetate

• Published in: Epilepsia (Copenhagen) Vol. 53; no. 6; pp. 935 - 946
• Main Authors: Bialer, Meir, Soares-da-Silva, Patricio
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2012; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: Animals; Anticonvulsants - chemistry; Anticonvulsants - pharmacokinetics; Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Antiepileptic drugs; Biological and medical sciences; Dibenzazepines - chemistry; Dibenzazepines - pharmacokinetics; Dibenzazepines - therapeutic use; Dose-Response Relationship, Drug; Drug Interactions; Drug therapy; Epilepsy - drug therapy; Eslicarbazepine; Eslicarbazepine acetate; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Medical sciences; Metabolic Networks and Pathways; Microsomes, Liver - drug effects; Microsomes, Liver - physiology; Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; Pharmacokinetics; Pharmacology. Drug treatments; Nervous system diseases; Epilepsy; Drug interactions; Eslicarbazepine acetate; Central nervous system disease; Anticonvulsant; Eslicarbazepine; Drug interaction; Sodium channel blocker; Pharmacokinetics; Antiepileptic drugs; Cerebral disorder
• ISSN: 0013-9580; 1528-1167; 1528-1167
• DOI: 10.1111/j.1528-1167.2012.03519.x

Summary 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.