Skip to main content
NCBI home page
Neurotherapeutics logoLink to Neurotherapeutics
. 2007 Jan;4(1):88–96. doi: 10.1016/j.nurt.2006.10.005

Eslicarbazepine acetate (BIA 2-093)

Luis Almeida 1, Patrício Soares-da-Silva 1,✉
PMCID: PMC7479690  PMID: 17199020

Summary

Eslicarbazepine acetate (ESL) [(S)-(−)-10-acetoxy-10, 11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide], formerly known as BIA 2-093, is a novel central nervous system (CNS)-active compound with anticonvulsant activity. It behaves as a voltage-gated sodium channel (VGSC) blocker and is currently under clinical development for the treatment of epilepsy and bipolar disorder. ESL shares with carbamazepine and oxcarbazepine 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. In pharmacokinetic studies in humans, ESL was rapidly and extensively metabolized to eslicarbazepine (S-licarbazepine), which is responsible for pharmacological activity. ESL has been tested in patients with refractory partial-onset seizures and was found to be efficacious and well tolerated. Monotherapy studies in adult epileptic patients and add-on studies in epileptic children are in the planning process. The efficacy and safety data appear to be very promising considering the refractory nature of the epileptic population enrolled in studies to date. Results of ongoing phase III studies in adult epileptic patients are expected to be available in 2007 and are required to define the position of ESL in the therapy of patients with epilepsy.

Key Words: Eslicarbazepine acetate, BIA 2-093, antiepileptic drugs, drug therapy, epilepsy

References

  • 1.Benes J, Parada A, Figueiredo AA, et al. Anticonvulsant and sodium channel-blocking properties of novel 10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide derivatives. J Med Chem. 1999;42:2582–2587. doi: 10.1021/jm980627g. [DOI] [PubMed] [Google Scholar]
  • 2.Parada A, Soares-da-Silva P. The novel anticonvulsant BIA 2-093 inhibits transmitter release during opening of voltage-gated sodium channels: a comparison with carbamazepine and oxcarbazepine. Neurochem Int. 2002;40:435–440. doi: 10.1016/S0197-0186(01)00101-2. [DOI] [PubMed] [Google Scholar]
  • 3.Bialer M. New antiepileptic drugs that are second generation to existing antiepileptic drugs. Expert Opin Investig Drugs. 2006;15:637–647. doi: 10.1517/13543784.15.6.637. [DOI] [PubMed] [Google Scholar]
  • 4.Almeida L, Soares-da-Silva P. Safety, tolerability and pharmaco-kinetic profile of BIA 2-093, a novel putative antiepileptic agent, during first administration to humans. Drugs R D. 2003;4:269–284. doi: 10.2165/00126839-200304050-00001. [DOI] [PubMed] [Google Scholar]
  • 5.Almeida L, Soares-da-Silva P. Safety, tolerability, and pharmacokinetic profile of BIA 2-093, a novel putative antiepileptic, in a rising multiple-dose study in young healthy humans. J Clin Pharmacol. 2004;44:906–918. doi: 10.1177/0091270004267591. [DOI] [PubMed] [Google Scholar]
  • 6.Fontes-Ribeiro C, Nunes T, Falcão A, et al. Eslicarbazepine acetate (BIA 2-093): relative bioavailability and bioequivalence of 50 mg/mL oral suspension and 200mg and 800mg tablet formulations. Drugs R D. 2005;6:253–260. doi: 10.2165/00126839-200506050-00001. [DOI] [PubMed] [Google Scholar]
  • 7.Bonifacio MJ, Sheridan RD, Parada A, Cunha RA, Patmore L, Soares-da-Silva P. Interaction of the novel anticonvulsant, BIA 2-093, with voltage-gated sodium channels: comparison with carbamazepine. Epilepsia. 2001;42:600–608. doi: 10.1046/j.1528-1157.2001.43600.x. [DOI] [PubMed] [Google Scholar]
  • 8.Ambrosio AF, Silva AP, Araujo I, et al. Neurotoxic/neuroprotective profile of carbamazepine, oxcarbazepine and two new putative antiepileptic drugs, BIA 2-093 and BIA 2-024. Eur J Pharmacol. 2000;406:191–201. doi: 10.1016/S0014-2999(00)00659-2. [DOI] [PubMed] [Google Scholar]
  • 9.Ambrosio AF, Silva AP, Malva JO, Soares-da-Silva P, Carvalho AP, Carvalho CM. Inhibition of glutamate release by BIA 2-093 and BIA 2-024, two novel derivatives of carbamazepine, due to blockade of sodium but not calcium channels. Biochem Pharmacol. 2001;61:1271–1275. doi: 10.1016/S0006-2952(01)00584-6. [DOI] [PubMed] [Google Scholar]
  • 10.Cunha RA, Coelho JE, Costenla AR, et al. Effects of carbamazepine and novel 10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide derivatives on synaptic transmission in rat hippocampal slices. Pharmacol Toxicol. 2002;90:208–213. doi: 10.1034/j.1600-0773.2002.900407.x. [DOI] [PubMed] [Google Scholar]
  • 11.Araujo IM, Ambrosio AF, Leal EC, et al. Neurotoxicity induced by antiepileptic drugs in cultured hippocampal neurons: a comparative study between carbamazepine, oxcarbazepine, and two new putative antiepileptic drugs, BIA 2-024 and BIA 2-093. Epilepsia. 2004;45:1498–1505. doi: 10.1111/j.0013-9580.2004.14104.x. [DOI] [PubMed] [Google Scholar]
  • 12.Bialer M, Johannessen S, Kupferberg HJ, Levy RH, Perucca E, Tomson T. Progress report on new antiepileptic drugs: a summary of the Seventh EILAT Conference (EILAT VII) Epilepsy Res. 2004;61:1–48. doi: 10.1016/j.eplepsyres.2004.07.010. [DOI] [PubMed] [Google Scholar]
  • 13.Sierra-Paredes G, Oreiro-Garcia MT, Nunez-Rodriguez A, Vazquez-Lopez A, Sierra-Marcuño G. Effect of novel anticonvulsant BIA 2-093 on seizures induced by picrotoxin microperfusion in the rat hippocampus. Epilepsia. 2004;45(Suppl 3):116–116. [Google Scholar]
  • 14.Sierra-Marcuño G, Oreiro-García MT, Vázquez-Illanes MD, Sierra-Paredes G. Effect of novel anticonvulsant BIA 2-093 on latrunculin A-induced seizures and extracellular glutamate concentrations in the rat hippocampus. Epilepsia. 2005;46(Suppl 8):302–302. doi: 10.1016/j.eplepsyres.2007.08.006. [DOI] [PubMed] [Google Scholar]
  • 15.Almeida L, Falcão A, Maia J, Mazur D, Gellert M, Soares-da-Silva P. Single-dose and steady-state pharmacokinetics of eslicarbazepine acetate (BIA 2-093) in healthy elderly and young subjects. J Clin Pharmacol. 2005;45:1062–1066. doi: 10.1177/0091270005279364. [DOI] [PubMed] [Google Scholar]
  • 16.Silveira P, Falcão A, Almeida L, Maia J, Soares-da-Silva P. BIA 2-093 pharmacokinetics in healthy elderly subjects. Epilepsia. 2004;45(Suppl 3):157–157. [Google Scholar]
  • 17.Soares-da-Silva P, Almeida L, Falcão A, Maia J. Effect of age and gender on the pharmacokinetics of eslicarbazepine acetate. Epilepsia. 2005;46(Suppl 8):216–217. [Google Scholar]
  • 18.Vaz-da-Silva M, Nunes T, Soares E, et al. Eslicarbazepine acetate pharmacokinetics after single and repeated doses in healthy subjects. Epilepsia. 2005;46(Suppl 8):191–191. [Google Scholar]
  • 19.Maia J, Vaz-da-Silva M, Almeida L, et al. Effect of food on the pharmacokinetic profile of eslicarbazepine acetate (BIA 2-093) Drugs R D. 2005;6:201–206. doi: 10.2165/00126839-200506040-00002. [DOI] [PubMed] [Google Scholar]
  • 20.EMEA-CPMP. Note for guidance on the investigation of bioavailability and bioequivalence. Presented at the European Agency for the Evaluation of Medicinal Products-Committee for Proprietary Medicinal Products, CPMP/EWP/QWP/1401/9; Jul 26, 2001. Available at: http://www.emea.eu.int/pdfs/human/ewp/140198en. pdf.
  • 21.Maia J, Almeida L, Vaz-da-Silva M, et al. Effect of eslicarbazepine acetate on the steady-state pharmacokinetics of digoxin in healthy subjects. Epilepsia. 2005;46(Suppl 8):178–179. [Google Scholar]
  • 22.Fattore C, Cipolla G, Gatti G, et al. Induction of ethinylestradiol and levonorgestrel metabolism by oxcarbazepine in healthy women. Epilepsia. 1999;40:783–787. doi: 10.1111/j.1528-1157.1999.tb00779.x. [DOI] [PubMed] [Google Scholar]
  • 23.Back DJ, Orme MLE. Pharmacokinetic drug interactions with oral contraceptives. Clin Pharmacokinet. 1990;18:472–484. doi: 10.2165/00003088-199018060-00004. [DOI] [PubMed] [Google Scholar]
  • 24.Fotherby K. Levonorgestrel: clinical pharmacokinetics. Clin Pharmacokinet. 1995;28:203–215. doi: 10.2165/00003088-199528030-00003. [DOI] [PubMed] [Google Scholar]
  • 25.Almeida L, Maia J, Soares-da-Silva P. A double-blind, add-on, placebo-controlled, exploratory trial of eslicarbazepine acetate in patients with partial-onset seizures. Epilepsia. 2005;46(Suppl 8):167–168. doi: 10.1111/j.1528-1167.2007.00984.x. [DOI] [PubMed] [Google Scholar]

Articles from Neurotherapeutics are provided here courtesy of Elsevier

RESOURCES