Identification
- Name
- Oxcarbazepine
- Accession Number
- DB00776 (APRD01308)
- Type
- Small Molecule
- Groups
- Approved
- Description
Oxcarbazepine is structurally a derivative of carbamazepine, adding an extra oxygen atom to the benzylcarboxamide group. This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine - sodium channel inhibition - and is generally used to treat partial seizures in epileptic children and adults.
- Structure
- Synonyms
- 10,11-Dihydro-10-oxo-5H-dibenz(b,f)azepine-5-carboxamide
- OCBZ
- Oxcarbamazepine
- Oxcarbazepina
- Oxcarbazepine
- Oxcarbazepinum
- External IDs
- GP 47680 / GP-47680 / KIN-493 / SPN-804
- Product Images
- Prescription Products
- Generic Prescription Products
- International/Other Brands
- Actinium / Barzepin / Carbox / Deprectal / Lonazet / Oxalepsy / Oxetol / Oxpin / Oxrate / Oxypine / Pharozepine / Prolepsi / Timox / Trexapin / Trileptin
- Categories
- Anti-epileptic Agent
- Anticonvulsants
- Carboxamide Derivatives
- Cardiovascular Agents
- Central Nervous System Agents
- Central Nervous System Depressants
- Chemically-Induced Disorders
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inducers (strong)
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strong)
- Cytochrome P-450 CYP3A5 Inducers
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Decreased Central Nervous System Disorganized Electrical Activity
- Dibenzazepines
- Enzyme Inducing Antiepileptic Drugs
- Membrane Transport Modulators
- Miscellaneous Anticonvulsants
- Nervous System
- P-glycoprotein/ABCB1 Inducers
- Sodium Channel Blockers
- UGT1A1 Inducers
- UGT1A1 Substrates
- Voltage-Gated Sodium Channel Blockers
- UNII
- VZI5B1W380
- CAS number
- 28721-07-5
- Weight
- Average: 252.268
Monoisotopic: 252.089877638 - Chemical Formula
- C15H12N2O2
- InChI Key
- CTRLABGOLIVAIY-UHFFFAOYSA-N
- InChI
- InChI=1S/C15H12N2O2/c16-15(19)17-12-7-3-1-5-10(12)9-14(18)11-6-2-4-8-13(11)17/h1-8H,9H2,(H2,16,19)
- IUPAC Name
- 9-oxo-2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3,5,7,11,13-hexaene-2-carboxamide
- SMILES
- NC(=O)N1C2=CC=CC=C2CC(=O)C2=C1C=CC=C2
Pharmacology
- Indication
For use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults with epilepsy and as adjunctive therapy in the treatment of partial seizures in children ages 4-16 with epilepsy.
- Associated Conditions
- Pharmacodynamics
Oxcarbazepine is structurally a derivative of carbamazepine, adding an extra oxygen atom to the benzylcarboxamide group. This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine - sodium channel inhibition - and is generally used to treat the same conditions.
- Mechanism of action
The exact mechanism by which oxcarbazepine exerts its anticonvulsant effect is unknown. It is known that the pharmacological activity of oxcarbazepine occurs primarily through its 10-monohydroxy metabolite (MHD). In vitro studies indicate an MHD-induced blockade of voltage-sensitive sodium channels, resulting in stabilization of hyperexcited neuronal membranes, inhibition of repetitive neuronal discharges, and diminution of propagation of synaptic impulses.
Target Actions Organism ASodium channel protein type 5 subunit alpha inhibitorHumans - Absorption
Completely absorbed following oral administration. Food has no effect on the rate and extent of absorption of oxcarbazepine. After single-dose administration of Trileptal tablets to healthy male volunteers under fasted conditions, the median tmax was 4.5 (range 3 to 13) hours. After single-dose administration of Trileptal oral suspension to healthy male volunteers under fasted conditions, the median tmax was six hours. Steady-state plasma concentrations of MHD are reached within 2-3 days in patients when Trileptal is given twice a day.
- Volume of distribution
- 49 L
- Protein binding
Approximately 40% of the active 10-monohydroxy metabolite (MHD) is bound to serum proteins, predominantly to albumin. Neither oxcarbazepine nor its MHD binds with alpha-1-acid glycoprotein.
- Metabolism
Oxcarbazepine is completely absorbed and extensively metabolized to its pharmacologically active 10-monohydroxy metabolite (MHD) by cytosolic enzymes. MHD is metabolized further by conjugation with glucuronic acid.
- Route of elimination
Oxcarbazepine is cleared from the body mostly in the form of metabolites which are predominantly excreted by the kidneys. Fecal excretion accounts for less than 4% of the administered dose.
- Half life
The half-life of the parent is about 2 hours, while the half-life of MHD is about 9 hours, so that MHD is responsible for most anti-epileptic activity.
- Clearance
- Not Available
- Toxicity
Isolated cases of overdose with oxcarbazepine have been reported. The maximum dose taken was approximately 24,000 mg. All patients recovered with symptomatic treatment.
- Affected organisms
- Humans and other mammals
- Pathways
Pathway Category Carbamazepine Metabolism Pathway Drug metabolism - Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details HLA class I histocompatibility antigen, B-15 alpha chain HLA-B*15:02 Not Available HLA-B*15 ADR Directly Studied Patients who carry this allele may be at an increased risk of Stevens-Johnson Syndrome and toxic epidermal necrolysis when treated with oxcarbazepine. Details
Interactions
- Drug Interactions
Drug Interaction (R)-warfarin The metabolism of (R)-warfarin can be increased when combined with Oxcarbazepine. (S)-Warfarin The metabolism of (S)-Warfarin can be increased when combined with Oxcarbazepine. 3-isobutyl-1-methyl-7H-xanthine Oxcarbazepine 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. 3,5-diiodothyropropionic acid The metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Oxcarbazepine. 4-hydroxycoumarin The metabolism of 4-hydroxycoumarin can be increased when combined with Oxcarbazepine. 4-Methoxyamphetamine The risk or severity of adverse effects can be increased when Oxcarbazepine is combined with 4-Methoxyamphetamine. 5-androstenedione The metabolism of 5-androstenedione can be increased when combined with Oxcarbazepine. 6-O-benzylguanine The metabolism of 6-O-benzylguanine can be increased when combined with Oxcarbazepine. 7-Deazaguanine Oxcarbazepine may increase the excretion rate of 7-Deazaguanine which could result in a lower serum level and potentially a reduction in efficacy. 7-ethyl-10-hydroxycamptothecin The metabolism of 7-ethyl-10-hydroxycamptothecin can be increased when combined with Oxcarbazepine. - Food Interactions
- Take without regard to meals. Avoid alcohol.
References
- Synthesis Reference
Judith Aronhime, "New crystal forms of oxcarbazepine and processes for their preparation." U.S. Patent US20030004154, issued January 02, 2003.
US20030004154- General References
- Mazza M, Della Marca G, Di Nicola M, Martinotti G, Pozzi G, Janiri L, Bria P, Mazza S: Oxcarbazepine improves mood in patients with epilepsy. Epilepsy Behav. 2007 May;10(3):397-401. Epub 2007 Feb 14. [PubMed:17300991]
- External Links
- Human Metabolome Database
- HMDB0014914
- KEGG Drug
- D00533
- KEGG Compound
- C07492
- PubChem Compound
- 34312
- PubChem Substance
- 46507580
- ChemSpider
- 31608
- BindingDB
- 34179
- ChEBI
- 7824
- ChEMBL
- CHEMBL1068
- Therapeutic Targets Database
- DAP000528
- PharmGKB
- PA450732
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Oxcarbazepine
- ATC Codes
- N03AF02 — Oxcarbazepine
- AHFS Codes
- 28:12.92 — Miscellaneous Anticonvulsants
- FDA label
- Download (195 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Ranbaxy laboratories ltd
- Novartis pharmaceuticals corp
- Apotex inc
- Breckenridge pharmaceutical inc
- Cadista pharmaceuticals inc
- Glenmark generics ltd
- Roxane laboratories inc
- Sun pharmaceutical industries ltd
- Taro pharmaceutical industries ltd
- Teva pharmaceuticals usa
- Packagers
- Amerisource Health Services Corp.
- Apotex Inc.
- Ascend Laboratories LLC
- Atlantic Biologicals Corporation
- Breckenridge Pharmaceuticals
- Bryant Ranch Prepack
- Cardinal Health
- Glenmark Generics Ltd.
- Innoviant Pharmacy Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Nexgen Pharma Inc.
- Novartis AG
- Nucare Pharmaceuticals Inc.
- PD-Rx Pharmaceuticals Inc.
- Physicians Total Care Inc.
- Ranbaxy Laboratories
- Rebel Distributors Corp.
- Remedy Repack
- Resource Optimization and Innovation LLC
- Roxane Labs
- Sandoz
- Southwood Pharmaceuticals
- Sun Pharmaceutical Industries Ltd.
- Taro Pharmaceuticals USA
- Teva Pharmaceutical Industries Ltd.
- Vangard Labs Inc.
- Dosage forms
Form Route Strength Suspension Oral 300 mg/5mL Suspension Oral 60 mg/1mL Tablet Oral 150 mg/1 Tablet Oral 300 mg/1 Tablet Oral 600 mg/1 Tablet, film coated Oral 150 mg/1 Tablet, film coated Oral 300 mg/1 Tablet, film coated Oral 600 mg/1 Tablet Oral 150 mg Tablet Oral 300 mg Tablet Oral 600 mg Suspension Oral 60 mg - Prices
Unit description Cost Unit OXcarbazepine 300 mg/5ml Suspension 250ml Bottle 162.03USD bottle Trileptal 600 mg tablet 7.05USD tablet Oxcarbazepine 600 mg tablet 5.06USD tablet Trileptal 300 mg tablet 3.84USD tablet Oxcarbazepine 300 mg tablet 2.75USD tablet Trileptal 150 mg tablet 2.1USD tablet Oxcarbazepine 150 mg tablet 1.53USD tablet Trileptal 300 mg/5ml Suspension 0.79USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) CA2277791 No 2008-11-18 2018-02-12 Canada US7037525 Yes 2006-05-02 2018-08-12 US US8119148 Yes 2012-02-21 2021-06-19 US US7910131 No 2011-03-22 2027-04-13 US US9119791 No 2015-09-01 2027-04-13 US US8821930 No 2014-09-02 2027-04-13 US US8617600 No 2013-12-31 2027-04-13 US US7722898 No 2010-05-25 2027-04-13 US US9370525 No 2016-06-21 2027-04-13 US US9351975 No 2016-05-31 2027-04-13 US US9855278 No 2018-01-02 2027-04-13 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 215.5 °C PhysProp water solubility 308 mg/L at 25 °C (SRC PhysProp estimated -- MEYLAN,WM et al. (1996)) Not Available logP 1.5 Not Available - Predicted Properties
Property Value Source Water Solubility 0.16 mg/mL ALOGPS logP 1.76 ALOGPS logP 1.82 ChemAxon logS -3.2 ALOGPS pKa (Strongest Acidic) 13.18 ChemAxon pKa (Strongest Basic) -4.3 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 2 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 63.4 Å2 ChemAxon Rotatable Bond Count 0 ChemAxon Refractivity 71.56 m3·mol-1 ChemAxon Polarizability 25.72 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9894 Blood Brain Barrier + 0.9975 Caco-2 permeable + 0.6299 P-glycoprotein substrate Non-substrate 0.7157 P-glycoprotein inhibitor I Non-inhibitor 0.7193 P-glycoprotein inhibitor II Non-inhibitor 0.9348 Renal organic cation transporter Non-inhibitor 0.8176 CYP450 2C9 substrate Non-substrate 0.773 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.6022 CYP450 1A2 substrate Non-inhibitor 0.7266 CYP450 2C9 inhibitor Non-inhibitor 0.7371 CYP450 2D6 inhibitor Non-inhibitor 0.9329 CYP450 2C19 inhibitor Non-inhibitor 0.7428 CYP450 3A4 inhibitor Non-inhibitor 0.8819 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8034 Ames test Non AMES toxic 0.5078 Carcinogenicity Non-carcinogens 0.9118 Biodegradation Not ready biodegradable 0.8977 Rat acute toxicity 1.9871 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9327 hERG inhibition (predictor II) Non-inhibitor 0.869
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
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
- Aryl alkyl ketones / Azepines / Benzenoids / Vinylogous amides / Isoureas / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Imines / Hydrocarbon derivatives
- Substituents
- Dibenzazepine / Aryl ketone / Aryl alkyl ketone / Azepine / Benzenoid / Vinylogous amide / Isourea / Ketone / Carboximidic acid derivative / Azacycle
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- cyclic ketone, dibenzoazepine (CHEBI:7824)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Voltage-gated sodium channel activity involved in sa node cell action potential
- Specific Function
- This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr...
- Gene Name
- SCN5A
- Uniprot ID
- Q14524
- Uniprot Name
- Sodium channel protein type 5 subunit alpha
- Molecular Weight
- 226937.475 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
- Vohora D, Saraogi P, Yazdani MA, Bhowmik M, Khanam R, Pillai KK: Recent advances in adjunctive therapy for epilepsy: focus on sodium channel blockers as third-generation antiepileptic drugs. Drugs Today (Barc). 2010 Apr;46(4):265-77. doi: 10.1358/dot.2010.46.4.1445795. [PubMed:20502724]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
- Lakehal F, Wurden CJ, Kalhorn TF, Levy RH: Carbamazepine and oxcarbazepine decrease phenytoin metabolism through inhibition of CYP2C19. Epilepsy Res. 2002 Dec;52(2):79-83. [PubMed:12458024]
- Turnheim K: [Drug interactions with antiepileptic agents]. Wien Klin Wochenschr. 2004 Feb 28;116(4):112-8. [PubMed:15038401]
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
- Bang L, Goa K: Oxcarbazepine: a review of its use in children with epilepsy. Paediatr Drugs. 2003;5(8):557-73. [PubMed:12895138]
- Andreasen AH, Brosen K, Damkier P: A comparative pharmacokinetic study in healthy volunteers of the effect of carbamazepine and oxcarbazepine on cyp3a4. Epilepsia. 2007 Mar;48(3):490-6. doi: 10.1111/j.1528-1167.2007.00924.x. [PubMed:17346248]
- Turnheim K: [Drug interactions with antiepileptic agents]. Wien Klin Wochenschr. 2004 Feb 28;116(4):112-8. [PubMed:15038401]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inducer
- 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
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
- Bang L, Goa K: Oxcarbazepine: a review of its use in children with epilepsy. Paediatr Drugs. 2003;5(8):557-73. [PubMed:12895138]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInducer
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1-1
- Molecular Weight
- 59590.91 Da
References
- Interactions [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inducer
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Scott LJ: Ledipasvir/Sofosbuvir: A Review in Chronic Hepatitis C. Drugs. 2018 Feb;78(2):245-256. doi: 10.1007/s40265-018-0864-z. [PubMed:29380288]
Drug created on June 13, 2005 07:24 / Updated on February 22, 2019 22:55