[Investigation on the hydroxylation metabolism of imrecoxib in vitro by using recombinant human CYPs].
OBJECTIVE
To identify the drug-metabolizing enzymes involved in the hydroxylation of the new anti-inflammatory and anodyne imrecoxib.


METHODS
Imrecoxib 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.


RESULTS
Imrecoxib is metabolized by CYP2C9, CYP2D6 and CYP3A4, with the rate of 62.5%, 21.1% and 16.4%, respectively.


CONCLUSIONS
CYP2C9 is the major enzyme involved in imrecoxib hydroxylation metabolism.
Li
Qiang
Q
Department of Pharmaceutical Microbiology, Shenyang Pharmaceutical University, Shenyang 110016, China.
Huang
Hai-Hua
HH
Dong
Yu
Y
Zhong
Da-Fang
DF
D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006900:Hydroxylation; D011758:Pyrroles / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013440:Sulfides / Q000378:metabolism*
D052246:Cyclooxygenase 2 Inhibitors; C488833:Imrecoxib; D011758:Pyrroles; D013440:Sulfides; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human