Inhibition of 1,3,8-trihydroxy-5-methoxyxanthone on cytochrome P450s.
- Author:
Wei CAO
1
;
Ya-jie CAO
;
Zhe-yi HU
;
Qi YU
;
Li-qing WANG
;
Gui-shan TAN
;
Ze-neng CHENG
Author Information
1. School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
- Publication Type:Journal Article
- MeSH:
Cytochrome P-450 Enzyme System;
metabolism;
Humans;
Microsomes, Liver;
drug effects;
enzymology;
Xanthones;
pharmacology
- From:
Journal of Central South University(Medical Sciences)
2006;31(6):858-861
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the inhibitive effects of 1,3,8-trihydroxy-5-methoxyxanthone (TMX) on cytochrome P450s (CYP450s) in human liver microsomes.
METHODS:Probe drugs were incubated with and without adding TMX to determine the changes of enzyme activities. The concentration ratio of metabolites to probe drugs was used to present enzyme activities. Concentrations of the probe drugs and their metabolites in the incubated mixture were detected by high performance liquid chromatography.
RESULTS:The variations (mean, 95%CI) of the activities of CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 were 2.95 x 10(-3) (2.03 x 10(-3), 3.88 x 10(-3)), 3.14 x 10(-2) (1.87 x 10(-2), 4.42 x 10(-2)), 2.27 x 10(-3) (-1.4 x 10(-2),1.81 x 10(-2)), 7.72 x 10(-2) (-0.83 x 10(-2), 0.2374), and -0.2548 (-2.9802, 2.4707), respectively. The activities of CYP1A2 and CYP2C9 were significantly reduced in the present of TMX.
CONCLUSION:TMX (10 micromol/L) has significant inhibitive effect on the activities of CYP1A2 and CYP2C9, but no significant inhibitive effect on the activities of CYP2C19, CYP2E1 and CYP3A4.
