Effects of Ciwujia Injection on four cytochrome P450 isoforms in rat liver microsomes in vitro

Abstract

Abstract: AIM: To investigate the effects of Ciwujia Injection on CYP2C9, CYP2D6, CYP2E1 and CYP3A4 in rat liver microsomes in vitro, providing references for clinical rational use of drug combination therapy.METHODS: Probe drugs of tolbutamide(TB), dextromethorphan(DM), chlorzoxazone(CLZ) and testosterone(TS) as well as Ciwujia Injection of different concentrations were added to incubation systems of rat liver microsomes in vitro, the concentrations of metabolites of the probe drugs in blank control, low, medium and high dose of Ciwujia Injection groups were determined by HPLC after incubation, and the differences of metabolic rates were compared to evaluate the effects of Ciwujia Injection on the activities of the four subtypes.The strength of inhibition (IC₅₀ and K_i values) was further determined if the activity in the medium dose group significantly decreased.RESULTS: Compared with the blank control group, the effects on CYP3A4 activity were statistically significant in low, medium and high dose groups of Ciwujia Injection (P<0.01), and the inhibition rates were 10.22%, 19.00%, 30.29%, with the IC₅₀ and K_i values were 3.96% and 2.74%(V/V); the activities of CYP2D6 were not statistically significant in low, medium and high dose groups (P>0.05); the activities of CYP2C9, CYP2E1 were not statistically significant in low dose groups (P>0.05), meanwhile the inhibitory effects on the two subtype activities in medium and high dose groups were statistically significant (P<0.05), but the rates of inhibition were less than 8.50% in the medium dose groups and less than 12.00% in the high dose groups.CONCLUSION: Ciwujia Injection exhibited inhibition against the activity of CYP3A4 in rat liver microsomes in vitro, with mixed inhibition model, and weak inhibition on CYP2C9, CYP2E1, but no effect on CYP2D6.

Key words: Ciwujia Injection, CYP450, Probe drug, Liver microsomes method, Inhibition

CLC Number:

R965.2

ZENG Chao, LIU Yan, LIU Gao-feng, LI Xiang. Effects of Ciwujia Injection on four cytochrome P450 isoforms in rat liver microsomes in vitro[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(2): 164-170.

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