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

Authors
Chauret, N Yergey, JA Brideau, C Friesen, RW Mancini, J Riendeau, D Silva, J Styhler, A Trimble, LA Nicoll-Griffith, DA
Citation
N. Chauret et al., In vitro metabolism considerations, including activity testing of metabolites, in the discovery and selection of the COX-2 inhibitor etoricoxib (MK-0663), BIOORG MED, 11(8), 2001, pp. 1059-1062
Citations number
20
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
8
Year of publication
2001
Pages
1059 - 1062
Database
ISI
SICI code
0960-894X(20010423)11:8<1059:IVMCIA>2.0.ZU;2-D
Abstract
Characterization of the metabolites of the COX-2 inhibitor etorieoxib (MK-0 663 and L-791,456) produced in vitro indicate formation of an N-oxide pyrid ine: and hydroxymethyl pyridine that van further be glucuronidated or oxidi zed to an acid. Significant turnover is observed in human hepatocytes. Seve ral 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 inhibi ts COX-I or contributes significantly to the inhibition of COX-2. (C) 2001 Published by Elsevier Science Ltd.