[Investigation on the hydroxylation metabolism of imrecoxib in vitro by using recombinant human CYPs]

Yao Xue Xue Bao. 2005 Oct;40(10):912-5.
[Article in Chinese]

Abstract

Aim: 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.

Conclusion: CYP2C9 is the major enzyme involved in imrecoxib hydroxylation metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Cyclooxygenase 2 Inhibitors
  • Imrecoxib
  • Pyrroles
  • Sulfides
  • Cytochrome P-450 Enzyme System
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human