PT - JOURNAL ARTICLE AU - Adam G. Staines AU - Michael W. H. Coughtrie AU - Brian Burchell TI - <em>N</em>-Glucuronidation of Carbamazepine in Human Tissues Is Mediated by UGT2B7 AID - 10.1124/jpet.104.073114 DP - 2004 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1131--1137 VI - 311 IP - 3 4099 - http://jpet.aspetjournals.org/content/311/3/1131.short 4100 - http://jpet.aspetjournals.org/content/311/3/1131.full SO - J Pharmacol Exp Ther2004 Dec 01; 311 AB - 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 μM 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. The American Society for Pharmacology and Experimental Therapeutics