In vitro metabolism considerations, including activity testing of metabolites, in the discovery and selection of the COX-2 inhibitor etoricoxib (MK-0663)

被引：42

作者：

Chauret, N ^{[1
]}

Yergey, JA ^{[1
]}

Brideau, C ^{[1
]}

Friesen, RW ^{[1
]}

Mancini, J ^{[1
]}

Riendeau, D ^{[1
]}

Silva, J ^{[1
]}

Styhler, A ^{[1
]}

Trimble, LA ^{[1
]}

Nicoll-Griffith, DA ^{[1
]}

机构：

[1] Merck Frosst Ctr Therapeut Res, Pointe Claire, PQ H9R 4P8, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 08期

关键词：

D O I：

10.1016/S0960-894X(01)00135-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Characterization of the metabolites of the COX-2 inhibitor etorieoxib (MK-0663 and L-791,456) produced in vitro indicate formation of an N-oxide pyridine: and hydroxymethyl pyridine that van further be glucuronidated or oxidized to an acid. Significant turnover is observed in human hepatocytes. Several CYPs are involved in the oxidative biotranformatiuns and. From in vitro studies, etoricoxib is not a potent CYP3A4 inducer or inhibitor. Based on an in vitro whole blood assay, none of the metabolites of etoricoxib inhibits COX-I or contributes significantly to the inhibition of COX-2. (C) 2001 Published by Elsevier Science Ltd.

引用

页码：1059 / 1062

页数：4

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