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

…, J Silva, A Styhler, LA Trimble, DA Nicoll-Griffith

文献索引：Chauret, Nathalie; Yergey, James A; Brideau, Christine; Friesen, Richard W; Mancini, Joseph; Riendeau, Denis; Silva, Jose; Styhler, Angela; Trimble, Laird A; Nicoll-Griffith, Deborah A Bioorganic and Medicinal Chemistry Letters, 2001 , vol. 11, # 8 p. 1059 - 1062

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被引用次数: 50

摘要

Characterization of the metabolites of the COX-2 inhibitor etoricoxib (MK-0663 and L- 791,456) produced in vitro indicate formation of an N-oxide pyridine and hydroxymethyl pyridine that can further be glucuronidated or oxidized to an acid. Significant turnover is observed in human hepatocytes. Several CYPs are involved in the oxidative biotranformations and, from in vitro studies, etoricoxib is not a potent CYP3A4 inducer or ...