[Inhibition of 1,3,8-trihydroxy-5-methoxyxanthone on cytochrome P450s].
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.


CONCLUSIONS
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.
Cao
Wei
W
School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
Cao
Ya-jie
YJ
Hu
Zhe-yi
ZY
Yu
Qi
Q
Wang
Li-qing
LQ
Tan
Gui-shan
GS
Cheng
Ze-neng
ZN
D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D044004:Xanthones / Q000494:pharmacology*
C582242:1,3,8-trihydroxy-5-methoxyxanthone; D044004:Xanthones; D003577:Cytochrome P-450 Enzyme System