Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of 3-hydroxydesloratadine

被引：30

作者：

Ghosal, A ^{[1
]}

Yuan, Y ^{[1
]}

Hapangama, N ^{[1
]}

Su, AD ^{[1
]}

Alvarez, N ^{[1
]}

Chowdhury, SK ^{[1
]}

Alton, KB ^{[1
]}

Patrick, JE ^{[1
]}

Zbaida, S ^{[1
]}

机构：

[1] Schering Plough Res Inst, Kenilworth, NJ 07033 USA

来源：

BIOPHARMACEUTICS & DRUG DISPOSITION | 2004年 / 25卷 / 06期

关键词：

desloratadine; UGT; glucuronides; UGT1A1; UGT1A3; UGT2B15;

D O I：

10.1002/bdd.405

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Desloratadine is a non-sedating antihistamine recently approved for the treatment of seasonal allergic rhinitis. The major metabolite of desloratadine in human plasma and urine is the glucuronide conjugate of 3-hydroxydesloratadine. 3-Hydroxydesloratadine-glucuronide is also the major in vitro metabolite of 3-hydroxydesloratadine formed by incubation of 3-hydroxydesloratadine with human liver microsomes supplemented with uridine 5'-diphosphate-glucuronic acid (UDPGA). The metabolite structure was confirmed by LC-MS and LC-MS/MS. Out of ten recombinant human UDP-glucuronosyltransferases (UGTs), UGT1A1, UGT1A3, UGT1A8 and UGT2B15 exhibited catalytic activity with respect to the formation of 3-hydroxydesloratadine-glucuronide. Inhibition studies with known inhibitors of UGT (diclofenac, flunitrazepam and bilirubin) confirmed the involvement of UGT1A1, UGT1A3 and UGT2B15 in the formation of 3-hydroxydesloratadine-glucuronide. The results from this study demonstrated that the in vitro formation of 3-hydroxydesloratadine-glucuronide from 3-hydroxydesloratadine was mediated via UGT1A1, UGT1A3 and UGT2B15 in human liver. Copyright (C) 2004 John Wiley Sons, Ltd.

引用

页码：243 / 252

页数：10

共 15 条

[11] The effect of incubation conditions on the enzyme kinetics of UDP-glucuronosyltransferases [J].