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Pathway Description
Carbamazepine Metabolism Pathway
Homo sapiens
Drug Metabolism Pathway
Carbamazepine is a drug used in the treatment of epilepsy, bipolar disorder, trigeminal neuralgia, and other psychiatric disorders. Carbamazepine is almost entirely metabolized in the liver, with the primary metabolic pathway being conversion to 10,11-epoxycarbamazepine. Ring hydroxylation to 2-hydroxycarbamazepine and 3-hydroxycarbamazepine represent a minor metabolic route, presumably though a carbamazepine 2,3-epoxide intermediate. Potential bioactivation occurs via CYP3A4-mediated secondary oxidation of 2-hydroxycarbamazepine to the potentially reactive carbamazepine iminoquinone and of 3-hydroxycarbamazepine to form other reactive metabolites. Radicals can also be formed from metabolism of 3-hydroxycarbamazepine by myeloperoxidase. Oxcarbazepine, an anticonvulsant used primarily in the treatment of epilepsy, is converted to 10,11-dihydroxycarbamazepine via 10-hydroxycarbazepine.
References
Carbamazepine Pathway References
[PharmgKB](http://www.pharmgkb.org/pathway/PA165817070)
Kanehisa M, Goto S, Sato Y, Furumichi M, Tanabe M: KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res. 2012 Jan;40(Database issue):D109-14. doi: 10.1093/nar/gkr988. Epub 2011 Nov 10.
Pubmed: 22080510
Lu W, Uetrecht JP: Peroxidase-mediated bioactivation of hydroxylated metabolites of carbamazepine and phenytoin. Drug Metab Dispos. 2008 Aug;36(8):1624-36. doi: 10.1124/dmd.107.019554. Epub 2008 May 7.
Pubmed: 18463199
Pearce RE, Uetrecht JP, Leeder JS: Pathways of carbamazepine bioactivation in vitro: II. The role of human cytochrome P450 enzymes in the formation of 2-hydroxyiminostilbene. Drug Metab Dispos. 2005 Dec;33(12):1819-26. doi: 10.1124/dmd.105.004861. Epub 2005 Aug 31.
Pubmed: 16135660
Pearce RE, Lu W, Wang Y, Uetrecht JP, Correia MA, Leeder JS: Pathways of carbamazepine bioactivation in vitro. III. The role of human cytochrome P450 enzymes in the formation of 2,3-dihydroxycarbamazepine. Drug Metab Dispos. 2008 Aug;36(8):1637-49. doi: 10.1124/dmd.107.019562. Epub 2008 May 7.
Pubmed: 18463198
Kim KA, Oh SO, Park PW, Park JY: Effect of probenecid on the pharmacokinetics of carbamazepine in healthy subjects. Eur J Clin Pharmacol. 2005 Jun;61(4):275-80. doi: 10.1007/s00228-005-0940-7. Epub 2005 May 25.
Pubmed: 15915352
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