In vitro Study on Herb-drug Interactions of Zuojin Pills Based on Cytochrome P450 / 中国药师

ABSTRACT

Objective: To explore the in vitro inhibition effect of Zuojin pills on 6 cytochrome P450 isoenzymes ( CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in human liver microsomes. Methods:The water extract of Zuojin pills, Cop-tidis Rhizoma and Euodiae Fructus was respectively incubated with human liver microsomes in the presence of seven probe substrates of CYP450 isoenzymes, and seven metabolites of cytochrome P450 probe substrate ( paracetamol/CYP1A2, 6α-hydroxypaclitaxel/CYP2C8, 4-hydroxydiclofenac/CYP2C9, 4-hydroxymephenytoin/CYP2C19, dextrorphan/CYP2D6, 6β-hydroxytestosterone/CYP3A4 and 1-hydroxymidazolam/CYP3A4) were simultaneously measured by LC-MS/MS, and the inhibitory effects were evaluated with IC50 value. Results:The IC50 value of Zuojin pills on CYP2D6, CYP1A2 and CYP3A4_T was 11. 6, 77. 4 and 97. 0 μg·ml-1 , respec-tively. The other IC50 values were from 334 to 690μg·ml-1 on CYP2C8, CYP2C9, CYP2C19 and CYP3A4_M isoenzymes. The IC50 value of Coptidis Rhizoma on CYP2D6, CYP1A2 and CYP3A4_T was 5. 8, 36. 8 and 59. 2 μg·ml-1 , respectively. The other IC50 values were from 163 to 476 μg·ml-1 on CYP2C8, CYP2C9, CYP2C19 and CYP3A4_M isoenzymes. The IC50 value of Euodiae Fructus on CYPs was over 107 μg·ml-1 . Conclusion:Zuojin pills shows notable inhibitory effect on CYP2D6, and weak inhibitory effects on CYP1A2 and CYP3A4_T. Coptidis Rhizoma has similar effects on CYPs and may be the main herbal medicine in the formu-la. Therefore, much attention should be paid to the combination of Zuojin pills and the drugs metabolized by human CYP2D6 in clin-ics.