N-glucuronidation of carbamazepine in human tissues is mediated by UGT2B7.
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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 ID
- 15292462 [ View in PubMed]
- Abstract
Carbamazepine (CBZ) is one of the most widely prescribed anticonvulsants despite a high incidence of idiosyncratic side effects. Metabolism of CBZ is complex, and of the more than 30 metabolites identified, one of the most abundant is CBZ N-glucuronide. To date the uridine diphosphate glucuronosyltransferase (UGT) isoform responsible for the N-glucuronidation of CBZ has not been identified. We have developed a sensitive liquid chromatography/mass spectrometry assay to quantify CBZ glucuronidation, and we report that CBZ is specifically glucuronidated by human UGT2B7. Kinetics of CBZ glucuronidation in human liver, kidney, and intestine microsomes were consistent with those of recombinant UGT2B7, which displayed a Km value of 214 microM and Vmax value of 0.79 pmol/mg/min. In addition to revealing the isoform responsible for CBZ glucuronidation, this is the first example of primary amine glucuronidation by UGT2B7.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Carbamazepine UDP-glucuronosyltransferase 2B7 Protein Humans UnknownSubstrateDetails