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

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Chauret N, Yergey JA, Brideau C, Friesen RW, Mancini J, Riendeau D, Silva J, Styhler A, Trimble LA, Nicoll-Griffith DA

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

Bioorg Med Chem Lett. 2001 Apr 23;11(8):1059-62.

PubMed ID

11327589 [ View in PubMed

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Abstract

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 inhibitor. Based on an in vitro whole blood assay, none of the metabolites of etoricoxib inhibits COX-1 or contributes significantly to the inhibition of COX-2.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Etoricoxib	Cytochrome P450 3A4	IC 50 (nM)	>50000	N/A	N/A	Details
Etoricoxib	Prostaglandin G/H synthase 2	IC 50 (nM)	1100	N/A	N/A	Details