Investigation on the hydroxylation metabolism of imrecoxib in vitro by using recombinant human CYPs.
- Author:
Qiang LI
1
;
Hai-Hua HUANG
;
Yu DONG
;
Da-Fang ZHONG
Author Information
- Publication Type:Journal Article
- MeSH: Aryl Hydrocarbon Hydroxylases; metabolism; Cyclooxygenase 2 Inhibitors; metabolism; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP2D6; metabolism; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; metabolism; Hydroxylation; Pyrroles; metabolism; Spectrometry, Mass, Electrospray Ionization; Sulfides; metabolism
- From: Acta Pharmaceutica Sinica 2005;40(10):912-915
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo identify the drug-metabolizing enzymes involved in the hydroxylation of the new anti-inflammatory and anodyne imrecoxib.
METHODSImrecoxib was incubated with heterologous expression human cytochrome P450 (rCYPs) in vitro, and metabolites and remained parent drug were detected with liquid chromatography-multistage mass spectrometry. The contribution of 4 CYPs in the hydroxylation metabolism of imrecoxib was evaluated by total normalized rate (TNR) method.
RESULTSImrecoxib is metabolized by CYP2C9, CYP2D6 and CYP3A4, with the rate of 62.5%, 21.1% and 16.4%, respectively.
CONCLUSIONCYP2C9 is the major enzyme involved in imrecoxib hydroxylation metabolism.
