CPUHY002对人肝微粒体CYP450酶体外抑制作用研究

The inhibitory effect of CPUHY002 on human liver cytochrome P450 enzyme in vitro

目的:评价CPUHY002在体外对人肝微粒体细胞色素P450(CYP450)酶6种亚型酶活性的影响。方法:将CPUHY002与CYP450酶6种亚型的特异性探针底物非那西丁、双氯酚酸钠、奥美拉唑、右美沙芬、氯唑沙宗、丙酸睾酮与人肝微粒体进行孵育,采用LC-MS/MS法测定对应6种代谢产物对乙酰氨基酚、4-羟基双氯酚酸、5-羟基奥美拉唑、右啡烷、6-羟基氯唑沙宗、6β-羟基睾酮的浓度,求算出IC50。结果:CPUHY002对CYP2C19和CYP2E1的IC50值分别为48.02μmol/L和47.19μmol/L,对CYP1A2、CYP2D6、CYP3A4和CYP2C9的IC50值>100μmol/L。结论:CPUHY002对于CYP2C19和CYP2E1具有弱抑制作用,对CYP1A2、CYP2D6、CYP3A4和CYP2C9无抑制作用。

Objective：To investigate the inhibitory effect of CPUHY002 on the activities of six human cytochrome P450 enzymes in vitro. Methods：The CPUHY002, six specific probe of cytochrome P450 enzymes （including phenacetin, sodium diclofenac, omeprazole, dextromethorphan, chlorzoxazone and testosterone propionate ） and human liver microsome were coineubated. The concentration of the six kinds of metabolites （ including aeetaminophen, 4-hydroxy dielofenac, 5-hydroxy omeprazole, dextrorphan, 6-hydroxy ehlorzoxazone and 6-hydroxy testosterone ） were analyzed by LC-MS/MS assay. The value of IC50 were calculated. Results： The IC50 values of CPUHY002 on CYP2C19 and CYP2E1 were 48.02 μmol/L and 47. 19 μmol/L, respectively. The IC50 values of CPUHY002 on CYP1A2, CYP2D6, CYP3A4 and CYP2C9 were more than 100 μ mol/L. Conclusions： The inhibitory effects of C PUHY002 on the activities of CYP2C19 and CYP2E1 are weak. CPUHY002 has not significant inhibitory effect on the activities of CYP1A2, CYP2D6, CYP3A4 and CYP2C9.