己烯雌酚对大鼠CYP2C6和CYP2D2酶的体外抑制作用

in vitro Inhibition of Diethylstilbestrol on CYP2C6 and CYP2C2 in Rats

目的研究己烯雌酚对大鼠肝微粒体中细胞色素P450同工酶2C6(CYP2C6)和2D2(CYP2D2)的抑制作用。方法采用探针底物法,使用液相色谱-串联质谱检测在不同浓度的己烯雌酚孵育体系中,CYP2C6和CYP2D2的特征性底物双氯芬酸与右美沙芬产生的代谢产物4’-羟基双氯芬酸与右啡烷的浓度。计算得到己烯雌酚对CYP2C6与CYP2D2的半数抑制浓度(IC50)。结果己烯雌酚对大鼠CYP2C6与CYP2D2的IC50值分别为(5.31±0.06)μmol/L,(7.03±0.01)μmol/L。结论己烯雌酚对大鼠CYP2C6与CYP2D2具有中等抑制作用,有必要进一步在体外人体水平对其进行评价以预防潜在的临床药物相互作用。

OBJECTIVE To evaluate the inhibition effect of diethylstilbestrol on CYP2C6 and CYP2D2 in rat liver microsomes.METHODS By adoption of probe substrate method,high performance liquid chromatography-tandem mass spectrometry was used to quantify the metabolites（ 4 ＇-hydroxydiclofenac and dextorphan） of the probe substrates（ diclofenac and dextromethorphan） for CYP2C6 and CYP2D2 respectively under different diethylstilbestrol levels. The half inhibition concentrations（ IC50） were then calculated. RESULTS The IC50 of diethylstilbestrol on CYP2C6 and CYP2D2 were（ 5. 31 ± 0. 06） μmol / L and（ 7. 03 ± 0. 01） μmol /L,respectively. CONCLUSION Diethylstilbestrol exhibited a moderate inhibition effect on rat CYP2C6 and CYP2D2. Further in vitro evaluation at human level is needed to avoid any potential clinical drug-drug interaction.