Identification

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Name
Carbamazepine
Accession Number
DB00564  (APRD00337)
Type
Small Molecule
Groups
Approved, Investigational
Description

Carbamazepine, also known as Tegretol, is an anticonvulsant drug and analgesic drug used to control seizures and to treat pain resulting from trigeminal neuralgia. It was initially approved by the FDA in 1965.3 Aside from the above uses, this drug is also given to control the symptoms of bipolar 1.16 Interestingly, carbamazepine was the first anticonvulsant used to treat individuals with bipolar disorder.6

Structure
Thumb
Synonyms
  • 5-Carbamoyl-5H-dibenz(b,f)azepine
  • 5-carbamoyl-5H-dibenz[b,f]azepine
  • 5-Carbamoyl-5H-dibenzo(b,f)azepine
  • 5-Carbamyl-5H-dibenzo(b,f)azepine
  • 5H-Dibenz(b,f)azepine-5-carboxamide
  • Carbamazepen
  • Carbamazepin
  • Carbamazepina
  • Carbamazépine
  • Carbamazepine
  • Carbamazepinum
  • CBZ
External IDs
G 32 883 / G-32883 / GEIGY 32883 / NSC-169864 / SPD417
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CarbamazepineTablet400 mg/1OralCaraco Pharmaceutical Laboratories, Ltd.2008-01-29Not applicableUs
CarbamazepineTablet300 mg/1OralCaraco Pharmaceutical Laboratories, Ltd.2008-01-29Not applicableUs
CarbamazepineTablet200 mg/1OralCaraco Pharmaceutical Laboratories, Ltd.2008-01-29Not applicableUs
CarbamazepineTablet100 mg/1OralCaraco Pharmaceutical Laboratories, Ltd.2008-01-29Not applicableUs
CarbamazepineTablet, chewable100 mg/1OralCaraco Pharmaceutical Laboratories, Ltd.2008-01-29Not applicableUs
CarbamazepineTablet, extended release200 mg/1OralKaiser Foundations Hospitals2009-10-282012-06-30Us
Carbamazepine 200 Tab 200mgTabletOralPro Doc Limitee1982-12-312013-07-15Canada
Carbamazepine 200mg TabletsTabletOralLaboratoires Confab IncNot applicableNot applicableCanada
Carbamazepine CRTablet, extended releaseOralPro Doc Limitee2013-11-21Not applicableCanada
Carbamazepine CRTablet, extended releaseOralPro Doc Limitee2013-11-21Not applicableCanada
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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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo Carbamazepine Tab 200mgTabletOralApotex Corporation1980-12-31Not applicableCanada
Apo-carbamazepine CRTablet, extended releaseOralApotex CorporationNot applicableNot applicableCanada
Apo-carbamazepine CRTablet, extended releaseOralApotex CorporationNot applicableNot applicableCanada
Bio-carbamazepineTabletOralBiomed Pharma2003-08-202010-03-16Canada
CarbamazepineTablet200 mg/1OralA S Medication Solutions1996-10-03Not applicableUs54569 265520180907 15195 j3bbid
CarbamazepineCapsule, extended release300 mg/1OralAvera McKennan Hospital2015-06-08Not applicableUs69189 041020180907 15195 1xwfejo
CarbamazepineTablet300 mg/1OralTorrent Pharmaceuticals Limited2005-12-072009-10-25Us
CarbamazepineCapsule, extended release300 mg/1OralNostrum Laboratories, Inc.2011-05-20Not applicableUs29033 0004 12 nlmimage10 c11360bb
CarbamazepineCapsule, extended release100 mg/1OralApotex Corp.2012-03-232023-03-31Us
CarbamazepineTablet200 mg/1OralRebel Distributors2009-07-01Not 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.

    Learn more
  • Product Code
    Product Code

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

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International/Other Brands
Actebral (Sanofi-Aventis) / Anleptic (Square) / Biston (Zentiva) / Carbamat (AstraZeneca) / Neurotop (Gerot) / TEGretol Chewtabs / TEGretol-CR (Novartis) / TEGretol-XR (Novartis) / Teril (Taro) / Timonil (Desitin) / Versitol (Micro Synapse) / Versizur (Micro Labs)
Categories
UNII
33CM23913M
CAS number
298-46-4
Weight
Average: 236.2686
Monoisotopic: 236.094963016
Chemical Formula
C15H12N2O
InChI Key
FFGPTBGBLSHEPO-UHFFFAOYSA-N
InChI
InChI=1S/C15H12N2O/c16-15(18)17-13-7-3-1-5-11(13)9-10-12-6-2-4-8-14(12)17/h1-10H,(H2,16,18)
IUPAC Name
2-azatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,9,11,13-heptaene-2-carboxamide
SMILES
NC(=O)N1C2=CC=CC=C2C=CC2=CC=CC=C12

Pharmacology

Indication

Carbamazepine is indicated for the treatment of epilepsy and pain associated with true trigeminal neuralgia.16 In particular, carbamazepine has shown efficacy in treating mixed seizures, partial seizures with complex symptoms, and generalized tonic-clonic seizures.3,16 Carbamazepine is also indicated for the treatment of manic episodes and mixed manic-depressive episodes caused by bipolar I disorder.16 Some off-label, unapproved uses of carbamazepine include the treatment of alcohol withdrawal syndrome and restless leg syndrome.9,10

Associated Conditions
Pharmacodynamics

General effects

Carbamazepine treats seizures and the symptoms of trigeminal neuralgia by inhibiting sodium channels. In bipolar 1 disorder, carbamazepine has been found to decrease mania symptoms in a clinically significant manner according to the Young Mania Rating Scale (YMRS).16 Carbamazepine has a narrow therapeutic index.3

A note on genetic variation and carbamazepine use

In studies of Han Chinese ancestry patients, a pronounced association between the HLA-B*1502 genotype and Steven Johnson syndrome and/or toxic epidermal necrolysis (SJS/TEN) resulting from carbamazepine use was observed.7

Mechanism of action

Carbamazepine's mechanism of action is not fully elucidated and is widely debated.5 One major hypothesis is that carbamazepine inhibits sodium channel firing, treating seizure activity. Animal research studies have demonstrated that carbamazepine exerts its effects by lowering polysynaptic nerve response and inhibiting post-tetanic potentiation. In both cats and rats, carbamazepine was shown to decrease pain caused by infraorbital nerve stimulation. A decrease in the action potential in the nucleus ventralis of the thalamus in the brain and inhibition of the lingual mandibular reflex were observed in other studies after carbamazepine use. Carbamazepine causes the above effects by binding to voltage-dependent sodium channels and preventing action potentials, which normally lead to stimulatory effects on nerves.8,15 In bipolar disorder, carbamazepine is thought to increase dopamine turnover and increase GABA transmission, treating manic and depressive symptoms.19

A common issue that has arisen is resistance to this drug in up to 30% of epileptic patients, which may occur to altered metabolism in patients with variant genotypes.13 A potential therapeutic target to combat carbamazepine resistance has recently been identified as the EPHX1 gene promoter, potentially conferring resistance to carbamazepine through methylation.14

TargetActionsOrganism
AVoltage-gated sodium channel alpha subunit
inhibitor
Humans
UNeuronal acetylcholine receptor subunit alpha-4Not AvailableHumans
UNuclear receptor subfamily 1 group I member 2
activator
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

The bioavailability of carbamazepine is in the range of 75-85% of an ingested dose.3 After one 200 mg oral extended-release dose of carbamazepine in a pharmacokinetic study, the Cmax carbamazepine was measured to be 1.9 ± 0.3 mcg/mL. The Tmax was 19 ± 7 hours. After several doses of 800 mg every 12 hours, the peak concentrations of carbamazepine were measured to be 11.0 ± 2.5 mcg/mL. The Tmax was reduced to 5.9 ± 1.8 hours. Extended-release carbamazepine demonstrated linear pharmacokinetics over a range of 200–800 mg.16

Effect of food on absorption

A meal containing high-fat content increased the rate of absorption of one 400 mg dose but not the AUC of carbamazepine.16 The elimination half-life remained unchanged between fed and fasting state. The pharmacokinetics of an extended-release carbamazepine dose was demonstrated to be similar when administered in the fasted state or with food.16 Based on these findings, food intake is unlikely to exert significant effects on carbamazepine absorption.

Volume of distribution

The volume of distribution of carbamazepine was found to be 1.0 L/kg in one pharmacokinetic study.4 Another study indicates that the volume of distribution of carbamazepine ranges between 0.7 to 1.4 L/kg.11. Carbamazepine crosses the placenta, and higher concentrations of this drug are found in the liver and kidney as opposed to lung and brain tissue.16 Carbamazepine crosses variably through the blood-brain barrier.13

Protein binding

Carbamazepine is 75%-80% bound to plasma proteins.3,16 One pharmacokinetic study indicates that it is 72% bound to plasma proteins.11

Metabolism

Carbamazepine is largely metabolized in the liver. CYP3A4 hepatic enzyme is the major enzyme that metabolizes carbamazepine to its active metabolite, carbamazepine-10,11-epoxide12, which is further metabolized to its trans-diol form by the enzyme epoxide hydrolase.16 Other hepatic cytochrome enzymes that contribute to the metabolism of carbamazepine are CYP2C8, CYP3A5, and CYP2B6.17 Carbamazepine also undergoes hepatic glucuronidation by UGT2B7 enzyme and several other metabolic reactions occur, resulting in the formation of minor hydroxy metabolites and quinone metabolites.17 Interestingly, carbamazepine induces its own metabolism.16 This leads to enhanced clearance, reduced half-life, and a reduction in serum levels of carbamazepine.3,16

Route of elimination

After an oral dose of radiolabeled carbamazepine, 72% of the administered radioactive dose was detected in the urine and the remainder of the ingested dose was found in the feces. Carbamazepine is mainly excreted as hydroxylated and conjugated metabolites, and minimal amounts of unchanged drug.16

Half life

The mean elimination half-life of carbamazepine was 35 to 40 hours after one dose of carbamazepine extended-release formulations. The half-life ranged from 12-17 hours after several doses of carbamazepine.16 One pharmacokinetic study determined the elimination half-life of carbamazepine to range between 27 to 36.8 hours in healthy volunteers.11

Clearance

In a pharmacokinetic study, the apparent oral clearance of carbamazepine was 25 ± 5 mL/min 11,16 after one dose of carbamazepine and 80 ± 30 mL/min after several doses.16

Toxicity

Toxicity information Oral LDLO (female): 1920 mg/kg/17W (intermittent); Oral LDLO (male): 54 mg/kg/9D (intermittent)18 Oral LD50 (rat): 1957 mg/kg 18

Overdose information

The initial signs of carbamazepine overdose occur 1-3 hours post ingestion. These signs and symptoms may vary in case of an overdose between carbamazepine and other drugs. Carbamazepine may cause various cardiovascular, neurological, respiratory, urinary symptoms as well as laboratory abnormalities including leukocytosis, reduced leucocytes, acetonuria, and glycosuria.16

Neuromuscular symptoms may occur initially, followed by mild cardiac symptoms such as tachycardia, hypertension, or hypotension. Higher doses of carbamazepine may cause more severed cardiovascular effects. Restlessness, muscular twitching, tremor, dilated pupils, nystagmus, psychomotor disturbances, and other neurological symptoms may occur. Hyperreflexia in the initial stages of overdose may be followed by hyporeflexia. Nausea, vomiting, urinary retention, dizziness or drowsiness may also occur.16 In cases of overdose, contact the local poison control center. Ensure to provide supportive and symptomatic treatment, which may include monitoring and careful supervision by a medical professional. The possibility of overdose with multiple drugs must be considered in the case of carbamazepine overdose. Maintain an adequate airway, oxygen, in addition to ventilation. Vital signs should be monitored.16

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Carbamazepine Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Heat shock 70 kDa protein 1-like---(C;T) / (T;T)T alleleADR Directly StudiedPatients with this genotype have increased risk of cutaneous hypersensitivity reactions with carbamazepine.Details
Heat shock 70 kDa protein 1A/1B---(C;C) / (C;G) / (C;T)C allele / C alleleADR Directly StudiedPatients with this genotype have increased risk of cutaneous hypersensitivity reactions with carbamazepine.Details
HLA class I histocompatibility antigen, B-15 alpha chain---(G;T) / (T;T)T alleleADR Directly StudiedPatients with this genotype have increased risk of cutaneous hypersensitivity reactions with carbamazepine.Details
HLA class I histocompatibility antigen, A-31 alpha chain---(C;G) / (G;G)G alleleADR Directly StudiedPatients with this genotype have increased risk of cutaneous hypersensitivity reactions with carbamazepine.Details
Promotilin---(A;A) / (A;C)A alleleADR Directly StudiedPatients with this genotype have increased risk of cutaneous hypersensitivity reactions with carbamazepine.Details
Sodium channel protein type 1 subunit alpha---(A;A) / (A;G)IVS5N + 5 G>AEffect Directly StudiedPatients with this genotype have increased resistance to the anti-epileptic effects of carbamazepine.Details
Flotillin-1HLA-B*1502(C;G) / (G;G)G > C / G > CADR Directly StudiedTaiwanese, Chinese, Indians, and Chinese–American patients with this genotype have increased risk of Stevens-Johnson syndrome or toxic epidermal necrolysis with carbamazepine.Details
Mucin-21HLA-B*1502(A;G) / (G;G)G>A / G>AADR Directly StudiedTaiwanese, Chinese, Indians, and Chinese–American patients with this genotype have increased risk of Stevens-Johnson syndrome or toxic epidermal necrolysis with carbamazepine.Details
HLA class I histocompatibility antigen, B-15 alpha chainHLA-B*15:02Not AvailableHLA-B*15ADR Directly StudiedPatients who carry this allele may be at an increased risk of Stevens-Johnson Syndrome and toxic epidermal necrolysis when treated with carbamazepine.Details
HLA class I histocompatibility antigen, A-3 alpha chainHLA-A*3101(A;T) / (T;T)A > TADR Directly StudiedPatients who carry this genotype in HLA-A are at a higher risk of experiencing a hypersensitivity reaction to carbamazepine.Details

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
(6R)-Folinic acidThe serum concentration of Carbamazepine can be decreased when it is combined with (6R)-Folinic acid.
(6S)-5,6,7,8-tetrahydrofolateThe serum concentration of Carbamazepine can be decreased when it is combined with (6S)-5,6,7,8-tetrahydrofolate.
(R)-warfarinThe metabolism of (R)-warfarin can be increased when combined with Carbamazepine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be increased when combined with Carbamazepine.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Carbamazepine is combined with 2-Methoxyethanol.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Carbamazepine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Carbamazepine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be decreased when it is combined with Carbamazepine.
3,5-diiodothyropropionic acidThe metabolism of Carbamazepine can be decreased when combined with 3,5-diiodothyropropionic acid.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Carbamazepine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
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
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Food Interactions
  • Avoid alcohol.
  • Avoid taking grapefruit or grapefruit juice throughout treatment.
  • Grapefruit can significantly increase serum levels of this product.
  • Take with food, increases availability and reduces irritation.

References

Synthesis Reference

Ketan Dhansukhlal Vyas, Wajid Sajjad Jafri, Ashok Krishna Kulkarni, "Process for preparing carbamazepine from iminostilbene." U.S. Patent US6245908, issued February, 1998.

US6245908
General References
  1. Staines AG, Coughtrie MW, Burchell B: N-glucuronidation of carbamazepine in human tissues is mediated by UGT2B7. J Pharmacol Exp Ther. 2004 Dec;311(3):1131-7. Epub 2004 Aug 3. [PubMed:15292462]
  2. Sisodiya SM, Goldstein DB: Drug resistance in epilepsy: more twists in the tale. Epilepsia. 2007 Dec;48(12):2369-70. [PubMed:18088268]
  3. Tolou-Ghamari Z, Zare M, Habibabadi JM, Najafi MR: A quick review of carbamazepine pharmacokinetics in epilepsy from 1953 to 2012. J Res Med Sci. 2013 Mar;18(Suppl 1):S81-5. [PubMed:23961295]
  4. Marino SE, Birnbaum AK, Leppik IE, Conway JM, Musib LC, Brundage RC, Ramsay RE, Pennell PB, White JR, Gross CR, Rarick JO, Mishra U, Cloyd JC: Steady-state carbamazepine pharmacokinetics following oral and stable-labeled intravenous administration in epilepsy patients: effects of race and sex. Clin Pharmacol Ther. 2012 Mar;91(3):483-8. doi: 10.1038/clpt.2011.251. Epub 2012 Jan 25. [PubMed:22278332]
  5. Ambrosio AF, Soares-Da-Silva P, Carvalho CM, Carvalho AP: Mechanisms of action of carbamazepine and its derivatives, oxcarbazepine, BIA 2-093, and BIA 2-024. Neurochem Res. 2002 Feb;27(1-2):121-30. [PubMed:11926264]
  6. Chen CH, Lin SK: Carbamazepine treatment of bipolar disorder: a retrospective evaluation of naturalistic long-term outcomes. BMC Psychiatry. 2012 May 23;12:47. doi: 10.1186/1471-244X-12-47. [PubMed:22620289]
  7. Johnson DL, Gellman H, Waters RL, Tognella M: Brachioradialis transfer for wrist extension in tetraplegic patients who have fifth-cervical-level neurological function. J Bone Joint Surg Am. 1996 Jul;78(7):1063-7. doi: 10.2106/00004623-199607000-00011. [PubMed:8698724]
  8. Kuo CC, Chen RS, Lu L, Chen RC: Carbamazepine inhibition of neuronal Na+ currents: quantitative distinction from phenytoin and possible therapeutic implications. Mol Pharmacol. 1997 Jun;51(6):1077-83. doi: 10.1124/mol.51.6.1077. [PubMed:9187275]
  9. Barrons R, Roberts N: The role of carbamazepine and oxcarbazepine in alcohol withdrawal syndrome. J Clin Pharm Ther. 2010 Apr;35(2):153-67. doi: 10.1111/j.1365-2710.2009.01098.x. [PubMed:20456734]
  10. Aurora RN, Kristo DA, Bista SR, Rowley JA, Zak RS, Casey KR, Lamm CI, Tracy SL, Rosenberg RS: The treatment of restless legs syndrome and periodic limb movement disorder in adults--an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice Guideline. Sleep. 2012 Aug 1;35(8):1039-62. doi: 10.5665/sleep.1988. [PubMed:22851801]
  11. Rawlins MD, Collste P, Bertilsson L, Palmer L: Distribution and elimination kinetics of carbamazepine in man. Eur J Clin Pharmacol. 1975 Feb 28;8(2):91-6. [PubMed:1233212]
  12. Yoshimura R, Yanagihara N, Terao T, Minami K, Toyohira Y, Ueno S, Uezono Y, Abe K, Izumi F: An active metabolite of carbamazepine, carbamazepine-10,11-epoxide, inhibits ion channel-mediated catecholamine secretion in cultured bovine adrenal medullary cells. Psychopharmacology (Berl). 1998 Feb;135(4):368-73. [PubMed:9539261]
  13. Thorn CF, Leckband SG, Kelsoe J, Leeder JS, Muller DJ, Klein TE, Altman RB: PharmGKB summary: carbamazepine pathway. Pharmacogenet Genomics. 2011 Dec;21(12):906-10. doi: 10.1097/FPC.0b013e328348c6f2. [PubMed:21738081]
  14. Lv Y, Zheng X, Shi M, Wang Z, Cui L: Different EPHX1 methylation levels in promoter area between carbamazepine-resistant epilepsy group and carbamazepine-sensitive epilepsy group in Chinese population. BMC Neurol. 2019 Jun 4;19(1):114. doi: 10.1186/s12883-019-1308-4. [PubMed:31164100]
  15. Jasdave S. Maan; Abdolreza Saadabadi (2019). Carbamazepine. Stat Pearls Publishing.
  16. Carbamazepine FDA Label [Link]
  17. Pharm KGB, carbamazepine pathway, pharmacokinetics [Link]
  18. Carbamazepine FDA label [Link]
  19. ipolar Disorders and Carbamazepine: Pharmacokinetics,Pharmacodynamics, Therapeutic Effects and Indications of Carbamazepine: Review of Articles [Link]
External Links
Human Metabolome Database
HMDB0014704
KEGG Drug
D00252
KEGG Compound
C06868
PubChem Compound
2554
PubChem Substance
46507583
ChemSpider
2457
BindingDB
50003659
ChEBI
3387
ChEMBL
CHEMBL108
Therapeutic Targets Database
DAP000129
PharmGKB
PA448785
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Carbamazepine
ATC Codes
N03AF01 — Carbamazepine
AHFS Codes
  • 28:12.92 — Miscellaneous Anticonvulsants
FDA label
Download (55.9 KB)
MSDS
Download (71.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableBio-equivalence Study / Fed Conditions1
1CompletedNot AvailableHealthy Volunteers3
1CompletedNot AvailableHealthy Volunteers / Pharmacology, Clinical1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentBipolar Disorder (BD) / Schizophrenic Disorders1
1CompletedTreatmentEpilepsies2
1CompletedTreatmentHealthy Participants1
1CompletedTreatmentHealthy Volunteers1
2CompletedTreatmentCocaine-Related Disorders1
2CompletedTreatmentCocaine-Related Disorders / Substance-Related Disorders2
2CompletedTreatmentEpilepsies / Infantile Spasms (IS)1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentPhotosensitive Epilepsy1
2RecruitingTreatmentAlpha-1-Antitrypsin Deficiency / Liver Cirrhosis1
2Unknown StatusPreventionChemotherapy-Induced Nausea and Vomiting (CINV)1
2, 3CompletedTreatmentBipolar Disorder (BD) / Depression, Bipolar1
2, 3CompletedTreatmentTrigeminal Neuralgia (TN)1
3CompletedNot AvailableSeizures1
3CompletedTreatmentBipolar Disorder (BD)2
3CompletedTreatmentEpilepsies4
3CompletedTreatmentEpilepsies / Monotherapy2
3CompletedTreatmentEpilepsies / Seizures1
3CompletedTreatmentEpilepsies / Partial onset seizure Epilepsy1
3CompletedTreatmentManic or Mixed Episode Associated With Bipolar I Disorder1
3RecruitingTreatmentDementias1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3Unknown StatusTreatmentSeizures, Epileptic / Strokes1
4CompletedNot AvailableConvulsions / Epilepsies / Osteopenia / Osteoporosis / Seizures1
4CompletedTreatmentAlcohol Dependence1
4CompletedTreatmentBipolar Disorder (BD)2
4CompletedTreatmentBipolar Disorder (BD) / Mania1
4CompletedTreatmentBipolar I Disorder2
4CompletedTreatmentBronchial Asthma2
4CompletedTreatmentCocaine-Related Disorders / Substance-Related Disorders1
4CompletedTreatmentDepression, Bipolar1
4CompletedTreatmentEpilepsies5
4CompletedTreatmentEpilepsy, Localization Related1
4CompletedTreatmentMetabolic Clearance Rate1
4CompletedTreatmentNeurocostal neuralgia / Pain, Neuropathic1
4CompletedTreatmentSeizures, Focal1
4Enrolling by InvitationTreatmentErythromelalgia1
4Not Yet RecruitingBasic ScienceBariatric Surgery Candidate1
4Not Yet RecruitingTreatmentBenign Childhood Epilepsy With Centrotemporal Spikes1
4Not Yet RecruitingTreatmentEpilepsy, Localization Related1
4RecruitingNot AvailableEpilepsies1
4RecruitingOtherContraception / Drug Drug Interaction (DDI)1
4RecruitingTreatmentBipolar Disorder (BD)1
4RecruitingTreatmentEpilepsies1
4Unknown StatusTreatmentBipolar Disorder (BD)1
Not AvailableCompletedNot AvailableEpilepsies3
Not AvailableCompletedBasic ScienceHealthy Male Volunteers1
Not AvailableCompletedTreatmentTraumatic Brain Injury (TBI)1
Not AvailableEnrolling by InvitationNot AvailableBipolar Disorder (BD)1
Not AvailableRecruitingNot AvailableEpilepsies1
Not AvailableUnknown StatusTreatmentAdults With Tonic Clonic Seizures and/or Partial Seizures1
Not AvailableUnknown StatusTreatmentCarpal Tunnel Syndrome (CTS) / Multiple Excitability Test1

Pharmacoeconomics

Manufacturers
  • Shire development inc
  • Validus pharmaceuticals inc
  • Taro pharmaceutical industries ltd
  • Wockhardt eu operations (swiss) ag
  • Novartis pharmaceuticals corp
  • Taro pharmaceuticals usa inc
  • Cadista pharmaceuticals inc
  • Torrent pharmaceuticals ltd
  • Teva pharmaceuticals usa inc
  • Actavis elizabeth llc
  • Apotex inc etobicoke site
  • Inwood laboratories inc sub forest laboratories inc
  • Pliva inc
  • Usl pharma inc
  • Warner chilcott div warner lambert co
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Ciba Geigy Ltd.
  • Coupler Enterprises Inc.
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • DSM Corp.
  • Goldline Laboratories Inc.
  • Hawkins Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Inwood Labs
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Neuman Distributors Inc.
  • Novartis AG
  • Nucare Pharmaceuticals Inc.
  • Patheon Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Packaging Center
  • Pharmacy Service Center
  • Physicians Total Care Inc.
  • Precision Dose Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Qualitest
  • Redpharm Drug
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Sandoz
  • Shire Inc.
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Taro Pharmaceuticals USA
  • Teva Pharmaceutical Industries Ltd.
  • Torpharm Inc.
  • Torrent Pharmaceuticals
  • Tya Pharmaceuticals
  • UDL Laboratories
  • Validus Pharmaceuticals
  • Vangard Labs Inc.
  • Vistapharm Inc.
  • Wellspring Pharmaceutical
  • Wockhardt Ltd.
  • Xactdose Inc.
Dosage forms
FormRouteStrength
Tablet, extended releaseOral
TabletOral
PowderNot applicable1 g/1g
SuspensionOral100 mg/5mL
SuspensionOral200 mg/10mL
TabletOral100 mg/1
TabletOral200 mg/1
TabletOral300 mg/1
TabletOral400 mg/1
Tablet, chewableOral100 mg/1
Tablet, chewableOral200 mg/1
Tablet, extended releaseOral400 mg/1
Injection, powder, for solutionIntravenous10 mg/1mL
Capsule, extended releaseOral100 mg/1
Capsule, extended releaseOral200 mg/1
Capsule, extended releaseOral300 mg/1
Tablet, chewableOral
SuspensionOral
Tablet, extended releaseOral100 mg/1
Tablet, extended releaseOral200 mg/1
Prices
Unit descriptionCostUnit
Equetro 300 mg capsule2.65USD capsule
TEGretol XR 400 mg 12 Hour tablet2.42USD tablet
Carbamazepine powder2.26USD g
Tegretol xr 400 mg tablet2.19USD tablet
Carbatrol 100 mg 12 Hour Capsule2.18USD capsule
Equetro 200 mg capsule2.15USD capsule
CarBAMazepine 400 mg 12 Hour tablet2.05USD tablet
Carbatrol 300 mg 12 Hour Capsule1.95USD capsule
Carbatrol 200 mg 12 Hour Capsule1.92USD capsule
Carbatrol er 100 mg capsule1.84USD capsule
Carbatrol er 200 mg capsule1.84USD capsule
Carbatrol er 300 mg capsule1.84USD capsule
Equetro 100 mg capsule1.74USD capsule
TEGretol XR 200 mg 12 Hour tablet1.45USD tablet
Tegretol xr 200 mg tablet1.1USD tablet
CarBAMazepine 200 mg 12 Hour tablet1.03USD tablet
TEGretol XR 100 mg 12 Hour tablet0.97USD tablet
Tegretol Cr 400 mg Sustained-Release Tablet0.84USD tablet
Tegretol 200 mg tablet0.75USD tablet
Tegretol xr 100 mg tablet0.55USD tablet
Tegretol Cr 200 mg Sustained-Release Tablet0.42USD tablet
Mylan-Carbamazepine Cr 400 mg Sustained-Release Tablet0.4USD tablet
Pms-Carbamazepine-Cr 400 mg Sustained-Release Tablet0.4USD tablet
Sandoz Carbamazepine Cr 400 mg Sustained-Release Tablet0.4USD tablet
Tegretol 200 mg Chewable Tablet0.34USD tablet
Carbamazepine 200 mg tablet0.31USD tablet
Epitol 200 mg tablet0.3USD tablet
CarBAMazepine 100 mg Chew Tabs0.25USD tab
Mylan-Carbamazepine Cr 200 mg Sustained-Release Tablet0.2USD tablet
Pms-Carbamazepine-Cr 200 mg Sustained-Release Tablet0.2USD tablet
Sandoz Carbamazepine Cr 200 mg Sustained-Release Tablet0.2USD tablet
Tegretol 100 mg Chewable Tablet0.17USD tablet
CarBAMazepine 100 mg/5ml Suspension0.16USD ml
Pms-Carbamazepine 200 mg Chewable Tablet0.16USD tablet
Sandoz Carbamazepine 200 mg Chewable Tablet0.16USD tablet
Taro-Carbamazepine 200 mg Chewable Tablet0.16USD tablet
Apo-Carbamazepine 200 mg Tablet0.08USD tablet
Novo-Carbamaz 200 mg Tablet0.08USD tablet
Nu-Carbamazepine 200 mg Tablet0.08USD tablet
Pms-Carbamazepine 100 mg Chewable Tablet0.08USD tablet
Sandoz Carbamazepine 100 mg Chewable Tablet0.08USD tablet
Taro-Carbamazepine 100 mg Chewable Tablet0.08USD tablet
Tegretol 20 mg/ml Suspension0.08USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5284662No1994-02-082011-02-08Us
US5912013No1999-06-152016-06-15Us
US6977253No2005-12-202024-05-19Us
US7635773No2009-12-222029-03-13Us
US8410077No2013-04-022029-03-13Us
US9493582No2016-11-152033-02-27Us
US9629797No2017-04-252028-11-10Us
US9770407No2017-09-262028-11-10Us
US9750822No2017-09-052029-03-13Us
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
melting point (°C)189-192https://www.lookchem.com/Carbamazepine/
boiling point (°C)399.6±45.0https://www.lookchem.com/Carbamazepine/
logP2.77http://www.t3db.ca/toxins/T3D2826
logS-3.2http://www.t3db.ca/toxins/T3D2826
pKa15.96, -3.8http://www.t3db.ca/toxins/T3D2826
Predicted Properties
PropertyValueSource
Water Solubility0.152 mg/mLALOGPS
logP2.1ALOGPS
logP2.77ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)15.96ChemAxon
pKa (Strongest Basic)-3.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.33 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity71.89 m3·mol-1ChemAxon
Polarizability25 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9962
Blood Brain Barrier+0.9958
Caco-2 permeable+0.6538
P-glycoprotein substrateNon-substrate0.6466
P-glycoprotein inhibitor INon-inhibitor0.8748
P-glycoprotein inhibitor IINon-inhibitor0.8381
Renal organic cation transporterNon-inhibitor0.8177
CYP450 2C9 substrateNon-substrate0.7466
CYP450 2D6 substrateSubstrate0.884
CYP450 3A4 substrateNon-substrate0.6204
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8222
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7358
Ames testNon AMES toxic0.5554
CarcinogenicityNon-carcinogens0.8848
BiodegradationNot ready biodegradable0.978
Rat acute toxicity2.1131 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9653
hERG inhibition (predictor II)Non-inhibitor0.8734
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.72 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0006-1910000000-4b2dc85e8da73b101ed2
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000i-0090000000-be63f70e101a786a369b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0910000000-f171a56d3bbeaef24ff4
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0900000000-a82def037961e9b94a9a
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0900000000-484ce005b4ae5d01fc2a
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0900000000-a6992953eac16c120e74
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-7a1010be5231131649eb
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0090000000-51ef94c86cca9b541780
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0490000000-4484ac1671912bc60ba9
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0910000000-e5ca06888593ada95f15
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-5742023f1e263fb40066
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-f27fb9d17b228cc328b8
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-63c554c485fd1d117082
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0090000000-c6c89d3e663885fcc080
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0490000000-8a1d8d7b932f1b0ad45e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0910000000-843efaf5294cb110e0b9
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-7eb2855f73a1ed729181
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-8a4709b0e827021ff3f9
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-1df850c9bb30bdd7c2e8
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-13a692d2c13ee8b68c2b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-83772c2db35186bf1ecc
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-b290173294be98d66006
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0910000000-19e4159c1f593ac5b7d2
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-771ef8e73ddaa54860b8
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0006-0900000000-c125faa4ad9fe14be82e
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0006-0900000000-3a27cd51304e5edfed4d
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-000l-0790000000-46b6d4ec5e29491b5c70
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-000l-0790000000-b259164c7da3679c2598
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000f-0930000000-b2a70bea75cef0c24556
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000f-1940000000-9677ddf985ba43e76817
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-2900000000-86f35079f274f4014c3d
MS/MS Spectrum - ESI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-ff23826da10bdf95f991
MS/MS Spectrum - APCI-ITFT , positiveLC-MS/MSsplash10-0006-0900000000-25b86b23833bee39c759
1H NMR Spectrum1D NMRNot Applicable

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 / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Dibenzazepine / Azepine / Benzenoid / Urea / Carbonic acid derivative / Azacycle / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Organic oxide
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
ureas, dibenzoazepine (CHEBI:3387)

Targets

Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity
Specific Function
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 protein forms a...

Components:
References
  1. Yang YC, Huang CS, Kuo CC: Lidocaine, carbamazepine, and imipramine have partially overlapping binding sites and additive inhibitory effect on neuronal Na+ channels. Anesthesiology. 2010 Jul;113(1):160-74. doi: 10.1097/ALN.0b013e3181dc1dd6. [PubMed:20526191]
  2. Yang YC, Kuo CC: Inhibition of Na(+) current by imipramine and related compounds: different binding kinetics as an inactivation stabilizer and as an open channel blocker. Mol Pharmacol. 2002 Nov;62(5):1228-37. [PubMed:12391287]
  3. Lipkind GM, Fozzard HA: Molecular model of anticonvulsant drug binding to the voltage-gated sodium channel inner pore. Mol Pharmacol. 2010 Oct;78(4):631-8. doi: 10.1124/mol.110.064683. Epub 2010 Jul 19. [PubMed:20643904]
  4. Rogawski MA, Loscher W: The neurobiology of antiepileptic drugs. Nat Rev Neurosci. 2004 Jul;5(7):553-64. doi: 10.1038/nrn1430. [PubMed:15208697]
  5. Carbamazepine FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Ligand-gated ion channel activity
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeabl...
Gene Name
CHRNA4
Uniprot ID
P43681
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-4
Molecular Weight
69956.47 Da
References
  1. Ortells MO, Barrantes GE: Molecular modelling of the interactions of carbamazepine and a nicotinic receptor involved in the autosomal dominant nocturnal frontal lobe epilepsy. Br J Pharmacol. 2002 Jul;136(6):883-95. doi: 10.1038/sj.bjp.0704786. [PubMed:12110613]
  2. Di Resta C, Ambrosi P, Curia G, Becchetti A: Effect of carbamazepine and oxcarbazepine on wild-type and mutant neuronal nicotinic acetylcholine receptors linked to nocturnal frontal lobe epilepsy. Eur J Pharmacol. 2010 Sep 15;643(1):13-20. doi: 10.1016/j.ejphar.2010.05.063. Epub 2010 Jun 16. [PubMed:20561518]
  3. Bertrand D: Neuronal Nicotinic Acetylcholine Receptors and Epilepsy. Epilepsy Curr. 2002 Nov;2(6):191-193. doi: 10.1046/j.1535-7597.2002.00072.x. [PubMed:15309115]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Activator
Curator comments
weak activator based on results of one in vitro study
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Faucette SR, Wang H, Hamilton GA, Jolley SL, Gilbert D, Lindley C, Yan B, Negishi M, LeCluyse EL: Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. Drug Metab Dispos. 2004 Mar;32(3):348-58. [PubMed:14977870]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Urichuk L, Prior TI, Dursun S, Baker G: Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab. 2008 Jun;9(5):410-8. [PubMed:18537577]
  2. Levy RH: Cytochrome P450 isozymes and antiepileptic drug interactions. Epilepsia. 1995;36 Suppl 5:S8-13. [PubMed:8806399]
  3. Cazali N, Tran A, Treluyer JM, Rey E, d'Athis P, Vincent J, Pons G: Inhibitory effect of stiripentol on carbamazepine and saquinavir metabolism in human. Br J Clin Pharmacol. 2003 Nov;56(5):526-36. [PubMed:14651727]
  4. Chen L, Boinpally R, Gad N, Greenberg WM, Wangsa J, Periclou A, Ghahramani P: Evaluation of Cytochrome P450 (CYP) 3A4-Based Interactions of Levomilnacipran with Ketoconazole, Carbamazepine or Alprazolam in Healthy Subjects. Clin Drug Investig. 2015 Oct;35(10):601-12. doi: 10.1007/s40261-015-0318-2. [PubMed:26315684]
  5. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  6. de Leon J, Santoro V, D'Arrigo C, Spina E: Interactions between antiepileptics and second-generation antipsychotics. Expert Opin Drug Metab Toxicol. 2012 Mar;8(3):311-34. doi: 10.1517/17425255.2012.660918. Epub 2012 Feb 15. [PubMed:22332980]
  7. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Cazali N, Tran A, Treluyer JM, Rey E, d'Athis P, Vincent J, Pons G: Inhibitory effect of stiripentol on carbamazepine and saquinavir metabolism in human. Br J Clin Pharmacol. 2003 Nov;56(5):526-36. [PubMed:14651727]
  2. Kato Y, Fujii T, Mizoguchi N, Takata N, Ueda K, Feldman MD, Kayser SR: Potential interaction between ritonavir and carbamazepine. Pharmacotherapy. 2000 Jul;20(7):851-4. [PubMed:10907977]
  3. Mesdjian E, Seree E, Charvet B, Mirrione A, Bourgarel-Rey V, Desobry A, Barra Y: Metabolism of carbamazepine by CYP3A6: a model for in vitro drug interactions studies. Life Sci. 1999;64(10):827-35. [PubMed:10096433]
  4. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  5. Liu A, Wang C, Hehir M, Zhou T, Yang J: In vivo induction of CYP in mice by carbamazepine is independent on PXR. Pharmacol Rep. 2015 Apr;67(2):299-304. doi: 10.1016/j.pharep.2014.10.002. Epub 2014 Oct 18. [PubMed:25712654]
  6. de Leon J, Santoro V, D'Arrigo C, Spina E: Interactions between antiepileptics and second-generation antipsychotics. Expert Opin Drug Metab Toxicol. 2012 Mar;8(3):311-34. doi: 10.1517/17425255.2012.660918. Epub 2012 Feb 15. [PubMed:22332980]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [PubMed:19754423]
  2. de Leon J, Santoro V, D'Arrigo C, Spina E: Interactions between antiepileptics and second-generation antipsychotics. Expert Opin Drug Metab Toxicol. 2012 Mar;8(3):311-34. doi: 10.1517/17425255.2012.660918. Epub 2012 Feb 15. [PubMed:22332980]
  3. Masubuchi Y, Nakano T, Ose A, Horie T: Differential selectivity in carbamazepine-induced inactivation of cytochrome P450 enzymes in rat and human liver. Arch Toxicol. 2001 Nov;75(9):538-43. [PubMed:11760814]
  4. Jerling M, Lindstrom L, Bondesson U, Bertilsson L: Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service. Ther Drug Monit. 1994 Aug;16(4):368-74. [PubMed:7974626]
  5. CYP table [Link]
  6. CP450 drug interactions [File]
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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  2. de Leon J, Santoro V, D'Arrigo C, Spina E: Interactions between antiepileptics and second-generation antipsychotics. Expert Opin Drug Metab Toxicol. 2012 Mar;8(3):311-34. doi: 10.1517/17425255.2012.660918. Epub 2012 Feb 15. [PubMed:22332980]
  3. Tegretol FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
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. 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]
  2. de Leon J, Santoro V, D'Arrigo C, Spina E: Interactions between antiepileptics and second-generation antipsychotics. Expert Opin Drug Metab Toxicol. 2012 Mar;8(3):311-34. doi: 10.1517/17425255.2012.660918. Epub 2012 Feb 15. [PubMed:22332980]
  3. Indiana University - Department of Medicine Clinical Pharmacology [Link]
  4. Drug Interactions & Labeling - FDA [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Pearce RE, Vakkalagadda GR, Leeder JS: Pathways of carbamazepine bioactivation in vitro I. Characterization of human cytochromes P450 responsible for the formation of 2- and 3-hydroxylated metabolites. Drug Metab Dispos. 2002 Nov;30(11):1170-9. [PubMed:12386121]
  2. de Leon J, Santoro V, D'Arrigo C, Spina E: Interactions between antiepileptics and second-generation antipsychotics. Expert Opin Drug Metab Toxicol. 2012 Mar;8(3):311-34. doi: 10.1517/17425255.2012.660918. Epub 2012 Feb 15. [PubMed:22332980]
  3. Pharm KGB, carbamazepine pathway, pharmacokinetics [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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
  1. Hidaka M, Okumura M, Fujita K, Ogikubo T, Yamasaki K, Iwakiri T, Setoguchi N, Arimori K: Effects of pomegranate juice on human cytochrome p450 3A (CYP3A) and carbamazepine pharmacokinetics in rats. Drug Metab Dispos. 2005 May;33(5):644-8. doi: 10.1124/dmd.104.002824. Epub 2005 Jan 26. [PubMed:15673597]
  2. Henshall J, Galetin A, Harrison A, Houston JB: Comparative analysis of CYP3A heteroactivation by steroid hormones and flavonoids in different in vitro systems and potential in vivo implications. Drug Metab Dispos. 2008 Jul;36(7):1332-40. doi: 10.1124/dmd.108.021279. Epub 2008 Apr 17. [PubMed:18420779]
  3. Park PW, Seo YH, Ahn JY, Kim KA, Park JY: Effect of CYP3A5*3 genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients. J Clin Pharm Ther. 2009 Oct;34(5):569-74. doi: 10.1111/j.1365-2710.2009.01057.x. [PubMed:19744012]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  5. Flockhart Table of Drug Interactions [Link]
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. Staines AG, Coughtrie MW, Burchell B: N-glucuronidation of carbamazepine in human tissues is mediated by UGT2B7. J Pharmacol Exp Ther. 2004 Dec;311(3):1131-7. Epub 2004 Aug 3. [PubMed:15292462]
  2. Puranik YG, Birnbaum AK, Marino SE, Ahmed G, Cloyd JC, Remmel RP, Leppik IE, Lamba JK: Association of carbamazepine major metabolism and transport pathway gene polymorphisms and pharmacokinetics in patients with epilepsy. Pharmacogenomics. 2013 Jan;14(1):35-45. doi: 10.2217/pgs.12.180. [PubMed:23252947]
  3. Pharm KGB, carbamazepine pathway, pharmacokinetics [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
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
  1. Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 3 lacks trans...
Gene Name
UGT1A6
Uniprot ID
P19224
Uniprot Name
UDP-glucuronosyltransferase 1-6
Molecular Weight
60750.215 Da
References
  1. Asai Y, Sakakibara Y, Nadai M, Katoh M: Effect of carbamazepine on expression of UDP-glucuronosyltransferase 1A6 and 1A7 in rat brain. Drug Metab Pharmacokinet. 2017 Dec;32(6):286-292. doi: 10.1016/j.dmpk.2017.09.002. Epub 2017 Oct 5. [PubMed:29158009]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A7
Uniprot ID
Q9HAW7
Uniprot Name
UDP-glucuronosyltransferase 1-7
Molecular Weight
59818.315 Da

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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
  1. Geick A, Eichelbaum M, Burk O: Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem. 2001 May 4;276(18):14581-7. Epub 2001 Jan 31. [PubMed:11297522]
  2. Owen A, Pirmohamed M, Tettey JN, Morgan P, Chadwick D, Park BK: Carbamazepine is not a substrate for P-glycoprotein. Br J Clin Pharmacol. 2001 Apr;51(4):345-9. [PubMed:11318771]
  3. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. [PubMed:12438524]
  4. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W: Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007 Feb;52(2):333-46. Epub 2006 Oct 10. [PubMed:17045309]
  5. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. [PubMed:12954186]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transmembrane transporter activity
Specific Function
Can activate specifically hydrolysis of GTP bound to RAC1 and CDC42, but not RALA. Mediates ATP-dependent transport of S-(2,4-dinitrophenyl)-glutathione (DNP-SG) and doxorubicin (DOX) and is the ma...
Gene Name
RALBP1
Uniprot ID
Q15311
Uniprot Name
RalA-binding protein 1
Molecular Weight
76062.86 Da
References
  1. Awasthi S, Hallene KL, Fazio V, Singhal SS, Cucullo L, Awasthi YC, Dini G, Janigro D: RLIP76, a non-ABC transporter, and drug resistance in epilepsy. BMC Neurosci. 2005 Sep 27;6:61. [PubMed:16188027]
  2. Pharm KGB, carbamazepine pathway, pharmacokinetics [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Ufer M, Mosyagin I, Muhle H, Jacobsen T, Haenisch S, Hasler R, Faltraco F, Remmler C, von Spiczak S, Kroemer HK, Runge U, Boor R, Stephani U, Cascorbi I: Non-response to antiepileptic pharmacotherapy is associated with the ABCC2 -24C>T polymorphism in young and adult patients with epilepsy. Pharmacogenet Genomics. 2009 May;19(5):353-62. [PubMed:19415824]
  2. Potschka H, Fedrowitz M, Loscher W: Brain access and anticonvulsant efficacy of carbamazepine, lamotrigine, and felbamate in ABCC2/MRP2-deficient TR- rats. Epilepsia. 2003 Dec;44(12):1479-86. [PubMed:14636316]

Drug created on June 13, 2005 07:24 / Updated on October 18, 2019 21:36