Identification

Name
Cenobamate
Accession Number
DB06119
Description

Cenobamate, or YKP-3089, is an antiepileptic drug developed by SK Pharmaceuticals and used to treat partial onset seizures.1,3 The exact mechanism of action has not been described in the literature, though it positively modulates GABAA and inhibits voltage gated sodium channels.3

Cenobamate was granted FDA approval on 21 November 2019.3

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 267.67
Monoisotopic: 267.0523023
Chemical Formula
C10H10ClN5O2
Synonyms
  • Cenobamate
  • Cénobamate
  • Cenobamato
  • Cenobamatum
External IDs
  • YKP-3089
  • YKP3089

Pharmacology

Indication

Cenobamate is indicated for the treatment of partial onset seizures in adults.3

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

The mechanism of cenobamate is unknown, however it modulates GABAA and inhibit voltage gated sodium channels.3 Cenobamate is given once daily and so it has a long duration of action.3 The therapeutic window is wide as doses of 750mg can be well tolerated.2 Patients should be counselled regarding the risk of DRESS syndrome, QT interval shortening, suicidal behavior, and neurological adverse effects.3

Mechanism of action

Cenobamate inhibits voltage gated sodium channels and is a positive GABAA modulator.3 However, the exact mechanism of action remains unknown.3 Inhibition of voltage gated sodium channels increases the threshold for generating action potentials and decreases the number of action potentials.1

Absorption

Cenobamate is 88% orally bioavailable with a Tmax of 1-4 hours.3 A high fat meal does not significantly impact the pharmacokinetics of cenobamate.3

Volume of distribution

The apparent volume of distribution of cenobamate is 40-50L.3

Protein binding

Cenobamate is 60% protein bound in plasma, mainly serum albumin.3

Metabolism

Data regarding the metabolism of cenobamate is lacking, however it is mostly glucuronidated by UGT2B7 and UGT2B4 or oxidized by a number of cytochromes.3

Route of elimination

Cenobamate is 87.8% eliminated in the urine and 5.2% in the feces.3

Half-life

The terminal half life of cenobamate is 50-60h.3

Clearance

The apparent oral clearance of cenobamate is 0.45-0.63L/h for a 100-400mg/day dose.3

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

There is limited information regarding the signs, symptoms, and treatment of a cenobamate overdose.3 Symptomatic and supportive treatment is recommended and there is limited data on the utility of dialysis to remove cenobamate from blood.3

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Cenobamate can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Cenobamate can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be decreased when it is combined with Cenobamate.
AbirateroneThe serum concentration of Cenobamate can be decreased when it is combined with Abiraterone.
AcalabrutinibThe metabolism of Cenobamate can be increased when combined with Acalabrutinib.
AcenocoumarolThe serum concentration of Acenocoumarol can be decreased when it is combined with Cenobamate.
AcetaminophenThe serum concentration of Cenobamate can be decreased when it is combined with Acetaminophen.
AdalimumabThe metabolism of Cenobamate can be increased when combined with Adalimumab.
AdemetionineThe metabolism of Cenobamate can be decreased when combined with Ademetionine.
AlbendazoleThe serum concentration of Albendazole can be decreased when it is combined with Cenobamate.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid alcohol. Alcohol may increase somnolence and sedation.
  • Take with or without food.

Products

International/Other Brands
XCopri
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
XcopriTablet, film coated150 mg/1OralSk Life Science, Inc.2020-03-12Not applicableUs
XcopriTablet, film coated100 mg/1OralSk Life Science, Inc.2020-03-12Not applicableUs
XcopriTablet, film coated200 mg/1OralSk Life Science, Inc.2020-03-12Not applicableUs
XcopriTablet, film coated50 mg/1OralSk Life Science, Inc.2020-03-12Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Xcopri Maintenance PackCenobamate (50 mg/1) + Cenobamate (200 mg/1)KitOralSk Life Science, Inc.2020-03-12Not applicableUs
Xcopri Maintenance PackCenobamate (150 mg/1) + Cenobamate (200 mg/1)KitOralSk Life Science, Inc.2020-03-12Not applicableUs
Xcopri Maintenance PackCenobamate (50 mg/1) + Cenobamate (200 mg/1)KitOralSk Life Science, Inc.2020-03-12Not applicableUs
Xcopri Maintenance PackCenobamate (150 mg/1) + Cenobamate (200 mg/1)KitOralSk Life Science, Inc.2020-03-12Not applicableUs
Xcopri Titration PackCenobamate (50 mg/1) + Cenobamate (100 mg/1)KitOralSk Life Science, Inc.2020-03-12Not applicableUs
Xcopri Titration PackCenobamate (12.5 mg/1) + Cenobamate (25 mg/1)KitOralSk Life Science, Inc.2020-03-12Not applicableUs
Xcopri Titration PackCenobamate (150 mg/1) + Cenobamate (200 mg/1)KitOralSk Life Science, Inc.2020-03-12Not applicableUs
Xcopri Titration PackCenobamate (50 mg/1) + Cenobamate (100 mg/1)KitOralSk Life Science, Inc.2020-03-12Not applicableUs
Xcopri Titration PackCenobamate (12.5 mg/1) + Cenobamate (25 mg/1)KitOralSk Life Science, Inc.2020-03-12Not applicableUs
Xcopri Titration PackCenobamate (150 mg/1) + Cenobamate (200 mg/1)KitOralSk Life Science, Inc.2020-03-12Not applicableUs

Categories

Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
P85X70RZWS
CAS number
913088-80-9
InChI Key
GFHAXPJGXSQLPT-VIFPVBQESA-N
InChI
InChI=1S/C10H10ClN5O2/c11-8-4-2-1-3-7(8)9(18-10(12)17)5-16-14-6-13-15-16/h1-4,6,9H,5H2,(H2,12,17)/t9-/m0/s1
IUPAC Name
(1R)-1-(2-chlorophenyl)-2-(2H-1,2,3,4-tetrazol-2-yl)ethyl carbamate
SMILES
NC(=O)O[C@@H](CN1N=CN=N1)C1=C(Cl)C=CC=C1

References

General References
  1. Nakamura M, Cho JH, Shin H, Jang IS: Effects of cenobamate (YKP3089), a newly developed anti-epileptic drug, on voltage-gated sodium channels in rat hippocampal CA3 neurons. Eur J Pharmacol. 2019 Jul 15;855:175-182. doi: 10.1016/j.ejphar.2019.05.007. Epub 2019 May 4. [PubMed:31063770]
  2. Kasteleijn-Nolst Trenite DGA, DiVentura BD, Pollard JR, Krauss GL, Mizne S, French JA: Suppression of the photoparoxysmal response in photosensitive epilepsy with cenobamate (YKP3089). Neurology. 2019 Aug 6;93(6):e559-e567. doi: 10.1212/WNL.0000000000007894. Epub 2019 Jul 10. [PubMed:31292226]
  3. FDA Approved Drug Products: Xcopri Cenobamate Oral Tablets [Link]
ChemSpider
10136642
RxNav
2265690
ChEMBL
CHEMBL3989949
Wikipedia
Cenobamate

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentEpilepsy, Localization Related1
3Enrolling by InvitationTreatmentPrimary Generalized Tonic Clonic Seizures in the Setting of Idiopathic Generalized Epilepsy1
3RecruitingTreatmentPrimary Generalized Epilepsy1
2Active Not RecruitingTreatmentEpilepsy, Localization Related2
2CompletedTreatmentEpilepsies1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentHealthy Volunteers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral50 mg/1
KitOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7598279No2009-10-062027-10-30Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility1.7mg/mLFDA Label
logP0.456ChemSpider
Predicted Properties
PropertyValueSource
Water Solubility0.936 mg/mLALOGPS
logP0.99ALOGPS
logP1.66ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)14.28ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area95.92 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity76.43 m3·mol-1ChemAxon
Polarizability24.35 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. FDA Approved Drug Products: Xcopri Cenobamate Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as...
Gene Name
UGT2B4
Uniprot ID
P06133
Uniprot Name
UDP-glucuronosyltransferase 2B4
Molecular Weight
60512.035 Da
References
  1. FDA Approved Drug Products: Xcopri Cenobamate Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. FDA Approved Drug Products: Xcopri Cenobamate Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. FDA Approved Drug Products: Xcopri Cenobamate Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. FDA Approved Drug Products: Xcopri Cenobamate Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. FDA Approved Drug Products: Xcopri Cenobamate Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. FDA Approved Drug Products: Xcopri Cenobamate Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. FDA Approved Drug Products: Xcopri Cenobamate Oral Tablets [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. FDA Approved Drug Products: Xcopri Cenobamate Oral Tablets [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: Xcopri Cenobamate Oral Tablets [Link]

Drug created on November 18, 2007 11:30 / Updated on June 12, 2020 10:52

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