Identification

Name
Eslicarbazepine acetate
Accession Number
DB09119
Type
Small Molecule
Groups
Approved
Description

Eslicarbazepine acetate (ESL) is an anticonvulsant medication approved for use in Europe, the United States and Canada as an adjunctive therapy for partial-onset seizures that are not adequately controlled with conventional therapy. Eslicarbazepine acetate is a prodrug that is rapidly converted to eslicarbazepine, the primary active metabolite in the body. Eslicarbazepine's mechanism of action is not well understood, but it is known that it does exert anticonvulsant activity by inhibiting repeated neuronal firing and stabilizing the inactivated state of voltage-gated sodium channels, thus preventing their return to the activated state during which seizure activity can occur.

Eslicarbazepine acetate is marketed as Aptiom in North America and Zebinix or Exalief in Europe. It is available in 200, 400, 600, or 800mg tablets that are taken once daily, with or without food. Eslicarbazepine acetate is associated with numerous side effects including dizziness, drowsiness, nausea, vomiting, diarrhea, headache, aphasia, lack of concentration, psychomotor retardation, speech disturbances, ataxia, depression and hyponatremia. It is recommended that patients taking eslicarbazepine acetate be monitored for suicidality.

Structure
Thumb
Synonyms
  • (10S)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide
  • (10S)-5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl acetate
  • ESL
  • Stedesa
External IDs
BIA 2-093 / BIA-2-093 / BIA2-093 / SEP 0002093 / SEP-0002093 / SEP0002093
Active Moieties
NameKindUNIICASInChI Key
EslicarbazepineprodrugS5VXA428R4104746-04-5BMPDWHIDQYTSHX-AWEZNQCLSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AptiomTablet600 mg/1OralSunovion2014-04-07Not applicableUs
AptiomTablet800 mgOralSunovion2014-08-07Not applicableCanada
AptiomTablet200 mgOralSunovion2014-08-07Not applicableCanada
AptiomTablet600 mgOralSunovion2014-08-07Not applicableCanada
AptiomTablet400 mg/1OralSunovion2014-04-07Not applicableUs
AptiomTablet800 mg/1OralSunovion2014-04-07Not applicableUs
AptiomTablet400 mgOralSunovion2014-08-07Not applicableCanada
AptiomTablet200 mg/1OralSunovion2014-04-07Not applicableUs
ZebinixTablet800 mgOralBial Portela & Cª, S.A.2009-04-21Not applicableEu
ZebinixTablet600 mgOralBial Portela & Cª, S.A.2009-04-21Not applicableEu
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AptiomEslicarbazepine acetate (400 mg/1) + Eslicarbazepine acetate (800 mg/1)KitOralSunovion2014-04-07Not applicableUs
AptiomEslicarbazepine acetate (400 mg/1) + Eslicarbazepine acetate (800 mg/1)KitOralSunovion2014-04-07Not applicableUs
International/Other Brands
Eksaliyef (Bial-Portela & Ca. S.A.) / Erelib (Bial-Portela & Ca. S.A.) / Eslicar (Emcure Pharmaceuticals Ltd) / Eslify (Torrent Pharmaceuticals Ltd) / Eslistar (Lupin Ltd) / Eslizen (Intas Pharmaceuticals Ltd) / Exalief (Bial-Portela & Ca. S.A.) / Normictal (Abbott India Ltd ) / Zebinix (Bial-Portela & Ca. S.A., Esai Co. Ltd.) / Zefretol (Sun Pharma Laboratories Ltd)
Categories
UNII
BEA68ZVB2K
CAS number
236395-14-5
Weight
Average: 296.326
Monoisotopic: 296.116092383
Chemical Formula
C17H16N2O3
InChI Key
QIALRBLEEWJACW-INIZCTEOSA-N
InChI
InChI=1S/C17H16N2O3/c1-11(20)22-16-10-12-6-2-4-8-14(12)19(17(18)21)15-9-5-3-7-13(15)16/h2-9,16H,10H2,1H3,(H2,18,21)/t16-/m0/s1
IUPAC Name
(9S)-2-carbamoyl-2-azatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-9-yl acetate
SMILES
CC(=O)O[C@H]1CC2=CC=CC=C2N(C(N)=O)C2=CC=CC=C12

Pharmacology

Indication

Eslicarbazepine acetate is indicated as adjunctive therapy in the treatment of partial-onset seizures that are not adequately controlled with conventional therapy in epileptic patients.

Associated Conditions
Pharmacodynamics

Eslicarbazepine acetate is associated with a dose- and concentration-dependant increase in heart rate and prolongation of PR interval.

Mechanism of action

Eslicarbazepine acetate is converted to the active metabolite eslicarbazepine which carries out its anticonvulsant activity. The exact mechanism of action is unknown, but it is thought to involve the inhibition of voltage-gated sodium channels. In in vitro electrophysiological studies, eslicarbazepine was shown to inhibit repeated neuronal firing by stabilizing the inactivated state of voltage-gated sodium channels and preventing their return to the activated state. In vitro studies also showed eslicarbazepine inhibiting T-type calcium channels, which likely also has a role in anticonvulsant activity.

TargetActionsOrganism
AP2X purinoceptor 4
antagonist
Human
Absorption

Eslicarbazepine active metabolite has a high bioavailability and reaches peak serum concentration 1-4 hours after a given dose. Eslicarbazepine acetate absorption is not affected by food.

Volume of distribution

The apparent volume of distribution of eslicarbazepine is 61.3 L for a body weight of 70 kg based on population PK analysis.

Protein binding

Eslicarbazepine is bound to plasma proteins at a relatively low rate of <40%, independent of concentration. In vitro studies have shown that plasma protein binding is not relevantly affected by the presence of other medications such as warfarin, diazepam, digoxin, phenytoin or tolbutamide. Similarly, the binding of these medications was not significantly affected by the presence of eslicarbazepine.

Metabolism

Eslicarbazepine acetate is rapidly and extensively metabolized to its major active metabolite, eslicarbazepine, via hydrolytic first-pass metabolism. Eslicarbazepine corresponds to about 92% of systemic exposure. Minor active metabolites (R)-licarbazepine and oxcarbazepine consist of <5% of systemic exposure. Active metabolites are then metabolized to inactive glucuronides that correspond to about 3% of systemic exposure.

Eslicarbazepine had a moderate inhibitory effect on CYP2C19 and a mild activation of UGT1A1-mediated glucuronidation when studied in human hepatic microsomes. It has been shown to induce CYP3A4 enzymes in vivo.

Route of elimination

Eslicarbazepine acetate and its metabolites are eliminated primarily via renal excretion. Eslicarbazepine active metabolite is excreted two-thirds in the unchanged form and one-third as a glucuronide conjugate. This accounts for around 90% of total metabolites excreted, with the remaining 10% being minor metabolites. Renal tubular reabsorption is expected to occur with eslicarbazepine.

Half life

The apparent plasma half-life of eslicarbazepine is 10-20 hours in healthy subjects and 13-20 hours in epilepsy patients. Steady-state plasma concentrations are attained after 4 to 5 days of once daily dosing.

Clearance

Renal clearance of eslicarbazepine was found to be approximately 20 mL/min in healthy subjects with normal renal function.

Toxicity

There are no adequate and well-controlled studies of the use of eslicarbazepine acetate in pregnant women. In studies conducted in pregnant mice, rats, and rabbits, eslicarbazepine acetate did show developmental toxicities, including teratogenicity, embryolethality, and fetal growth retardation, at clinically relevant doses. Drug-induced liver injury ranging from mild to moderate elevations in transaminases (>3 times the upper limit of normal) to rare cases with concomitant elevations of total bilirubin (>2 times the upper limit of normal) have been reported with the use of eslicarbazepine. Overdose with eslicarbazepine acetate appears similar to its known adverse reactions and includes symptoms of hyponatremia, dizziness, nausea, vomiting, somnolence, euphoria, oral paraesthesias, ataxia, and diplopia. There is no specific antidote for eslicarbazepine acetate overdose and it should be treated primarily with supportive measures. If required, the drug may be removed by gastric lavage, partially by hemodialysis or inactivated with activated charcoal.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Eslicarbazepine acetate.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Eslicarbazepine acetate.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Eslicarbazepine acetate is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineEslicarbazepine acetate may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Eslicarbazepine acetate.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Eslicarbazepine acetate.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Eslicarbazepine acetate.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Eslicarbazepine acetate.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Eslicarbazepine acetate.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Eslicarbazepine acetate.
Food Interactions
Not Available

References

Synthesis Reference
  • Ravinder B, Reddy SR, Sridhar M, Mohan MM, Srinivas K, Reddy AP, Bandichhor R. An efficient synthesis for eslicarbazepine acetate, oxcarbazepine, and carbamazepine. Tetrahedron Letters. 2013 May 29;54(22):2841-4.
  • Desai S, Poddar A, Sawant K: Formulation of cyclodextrin inclusion complex-based orally disintegrating tablet of eslicarbazepine acetate for improved oral bioavailability. Mater Sci Eng C Mater Biol Appl. 2016 Jan 1;58:826-34. doi: 10.1016/j.msec.2015.09.019. Epub 2015 Sep 8. Pubmed.
General References
  1. Banach M, Borowicz KK, Czuczwar SJ: Pharmacokinetic/pharmacodynamic evaluation of eslicarbazepine for the treatment of epilepsy. Expert Opin Drug Metab Toxicol. 2015 Apr;11(4):639-48. doi: 10.1517/17425255.2015.1021686. Epub 2015 Mar 5. [PubMed:25740561]
  2. Bialer M, White HS: Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov. 2010 Jan;9(1):68-82. doi: 10.1038/nrd2997. [PubMed:20043029]
  3. 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:22612290]
  4. Villanueva V, Serratosa JM, Guillamon E, Garces M, Giraldez BG, Toledo M, Salas-Puig J, Lopez Gonzalez FJ, Flores J, Rodriguez-Uranga J, Castillo A, Mauri JA, Camacho JL, Lopez-Gomariz E, Giner P, Torres N, Palau J, Molins A: Long-term safety and efficacy of eslicarbazepine acetate in patients with focal seizures: results of the 1-year ESLIBASE retrospective study. Epilepsy Res. 2014 Sep;108(7):1243-52. doi: 10.1016/j.eplepsyres.2014.04.014. Epub 2014 May 14. [PubMed:24908564]
  5. Soares-da-Silva P, Pires N, Bonifacio MJ, Loureiro AI, Palma N, Wright LC: Eslicarbazepine acetate for the treatment of focal epilepsy: an update on its proposed mechanisms of action. Pharmacol Res Perspect. 2015 Mar;3(2):e00124. doi: 10.1002/prp2.124. Epub 2015 Mar 30. [PubMed:26038700]
  6. Rocamora R: A review of the efficacy and safety of eslicarbazepine acetate in the management of partial-onset seizures. Ther Adv Neurol Disord. 2015 Jul;8(4):178-86. doi: 10.1177/1756285615589711. [PubMed:26136845]
  7. Tomic MA, Pecikoza UB, Micov AM, Stepanovic-Petrovic RM: The Efficacy of Eslicarbazepine Acetate in Models of Trigeminal, Neuropathic, and Visceral Pain: The Involvement of 5-HT1B/1D Serotonergic and CB1/CB2 Cannabinoid Receptors. Anesth Analg. 2015 Dec;121(6):1632-9. doi: 10.1213/ANE.0000000000000953. [PubMed:26465930]
  8. Jacobson MP, Pazdera L, Bhatia P, Grinnell T, Cheng H, Blum D: Efficacy and safety of conversion to monotherapy with eslicarbazepine acetate in adults with uncontrolled partial-onset seizures: a historical-control phase III study. BMC Neurol. 2015 Mar 28;15:46. doi: 10.1186/s12883-015-0305-5. [PubMed:25880756]
  9. Zaccara G, Giovannelli F, Cincotta M, Carelli A, Verrotti A: Clinical utility of eslicarbazepine: current evidence. Drug Des Devel Ther. 2015 Feb 10;9:781-9. doi: 10.2147/DDDT.S57409. eCollection 2015. [PubMed:25709402]
  10. Sperling MR, Abou-Khalil B, Harvey J, Rogin JB, Biraben A, Galimberti CA, Kowacs PA, Hong SB, Cheng H, Blum D, Nunes T, Soares-da-Silva P: Eslicarbazepine acetate as adjunctive therapy in patients with uncontrolled partial-onset seizures: Results of a phase III, double-blind, randomized, placebo-controlled trial. Epilepsia. 2015 Feb;56(2):244-53. doi: 10.1111/epi.12894. Epub 2014 Dec 22. [PubMed:25528898]
  11. Shaikh S, Rizvi SM, Hameed N, Biswas D, Khan M, Shakil S, Kamal MA: Aptiom (eslicarbazepine acetate) as a dual inhibitor of beta-secretase and voltage-gated sodium channel: advancement in Alzheimer's disease-epilepsy linkage via an enzoinformatics study. CNS Neurol Disord Drug Targets. 2014;13(7):1258-62. [PubMed:25230222]
  12. Doeser A, Soares-da-Silva P, Beck H, Uebachs M: The effects of eslicarbazepine on persistent Na(+) current and the role of the Na(+) channel beta subunits. Epilepsy Res. 2014 Feb;108(2):202-11. doi: 10.1016/j.eplepsyres.2013.11.022. Epub 2013 Dec 8. [PubMed:24368131]
External Links
KEGG Drug
D09612
PubChem Compound
179344
PubChem Substance
310265036
ChemSpider
156110
BindingDB
50240669
ChEBI
87016
ChEMBL
CHEMBL87992
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Eslicarbazepine_acetate
AHFS Codes
  • 28:12.92 — Miscellaneous Anticonvulsants
FDA label
Download (820 KB)
MSDS
Download (44.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentEpilepsies25
1CompletedTreatmentEpilepsy, Localization Related2
1CompletedTreatmentPain, Neuropathic1
1TerminatedTreatmentEpilepsies2
2CompletedNot AvailableEpilepsies1
2CompletedTreatmentBipolar I Disorder2
2CompletedTreatmentEpilepsies2
2CompletedTreatmentEpilepsy, Localization Related1
2CompletedTreatmentFibromyalgia1
2CompletedTreatmentMigraines1
2CompletedTreatmentPainful Diabetic Neuropathy (PDN)1
2CompletedTreatmentPostherpetic Neuralgia1
2TerminatedTreatmentBipolar I Disorder1
3Active Not RecruitingTreatmentEpilepsy, Localization Related1
3Active Not RecruitingTreatmentPartial Epilepsy in Children and Adolescents1
3CompletedTreatmentEpilepsies4
3CompletedTreatmentEpilepsy With Simple or Complex Partial Onset Seizures1
3CompletedTreatmentEpilepsy, Localization Related2
3CompletedTreatmentRefractory Partial Epilepsy1
3TerminatedTreatmentPainful Diabetic Neuropathy (PDN)1
3TerminatedTreatmentPost-Herpetic Neuralgia (PHN)1
3WithdrawnTreatmentEpilepsies1
4CompletedTreatmentEpilepsies2
4RecruitingTreatmentEpilepsy With Partial On-set Seizures1
Not AvailableCompletedNot AvailableEpilepsies2
Not AvailableCompletedNot AvailablePartial onset seizure Epilepsy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
KitOral
TabletOral200 mg
TabletOral200 mg/1
TabletOral400 mg/1
TabletOral400 mg
TabletOral600 mg/1
TabletOral600 mg
TabletOral800 mg/1
TabletOral800 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5753646No1996-06-272016-06-27Us
US8372431No2010-04-172030-04-17Us
US9206135No2006-04-212026-04-21Us
US9643929No2006-04-212026-04-21Us
US9566244No2008-10-232028-10-23Us
US9763954No2008-09-132028-09-13Us
US9750747No2012-08-242032-08-24Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityWater solubility of eslicarbazepine acetate is low at less than 1 mg/mL including at different pH values. Its main metabolite eslicarbazepine has a greater water solubility of 4.2 mg/mL.# Banach M, Borowicz KK, Czuczwar SJ: Pharmacokinetic/pharmacodynamic evaluation of eslicarbazepine for the treatment of epilepsy. Expert Opin Drug Metab Toxicol. 2015 Apr;11(4):639-48. doi: 10.1517/17425255.2015.1021686. Epub 2015 Mar 5. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/25740561
logP8.8# 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":http://www.ncbi.nlm.nih.gov/pubmed/22612290
Predicted Properties
PropertyValueSource
Water Solubility0.11 mg/mLALOGPS
logP1.99ALOGPS
logP2.17ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)15.96ChemAxon
pKa (Strongest Basic)-3.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area72.63 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity81.44 m3·mol-1ChemAxon
Polarizability30.19 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as dibenzazepines. These are compounds with two benzene rings connected by an azepine ring. Azepine is an unsaturated seven-member heterocycle with one nitrogen atom replacing a carbon atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzazepines
Sub Class
Dibenzazepines
Direct Parent
Dibenzazepines
Alternative Parents
Azepines / Benzenoids / Ureas / Carboxylic acid esters / Monocarboxylic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
Dibenzazepine / Azepine / Benzenoid / Carboxylic acid ester / Urea / Carbonic acid derivative / Carboxylic acid derivative / Monocarboxylic acid or derivatives / Azacycle / Organic nitrogen compound
show 8 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
acetate ester, carboxamide, dibenzoazepine (CHEBI:87016)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Receptor for ATP that acts as a ligand-gated ion channel. This receptor is insensitive to the antagonists PPADS and suramin.
Gene Name
P2RX4
Uniprot ID
Q99571
Uniprot Name
P2X purinoceptor 4
Molecular Weight
43368.725 Da
References
  1. Tian M, Abdelrahman A, Weinhausen S, Hinz S, Weyer S, Dosa S, El-Tayeb A, Muller CE: Carbamazepine derivatives with P2X4 receptor-blocking activity. Bioorg Med Chem. 2014 Feb 1;22(3):1077-88. doi: 10.1016/j.bmc.2013.12.035. Epub 2013 Dec 25. [PubMed:24411477]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. 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:22612290]
  2. Bialer M, White HS: Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov. 2010 Jan;9(1):68-82. doi: 10.1038/nrd2997. [PubMed:20043029]
  3. Galiana GL, Gauthier AC, Mattson RH: Eslicarbazepine Acetate: A New Improvement on a Classic Drug Family for the Treatment of Partial-Onset Seizures. Drugs R D. 2017 Sep;17(3):329-339. doi: 10.1007/s40268-017-0197-5. [PubMed:28741150]
  4. Eslicarbazepine, PDR [Link]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. 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:22612290]
  2. Bialer M, White HS: Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov. 2010 Jan;9(1):68-82. doi: 10.1038/nrd2997. [PubMed:20043029]

Drug created on September 22, 2015 14:02 / Updated on November 13, 2018 08:05