藁本内酯在大鼠肝微粒体中代谢的酶动力学

研究体外大鼠肝微粒体藁本内酯代谢的酶动力学及选择性CYP450酶抑制剂对其代谢的影响。建立测定肝微粒体孵育液中藁本内酯含量的LC-MS法，以尼群地平为内标，二者的定量离子m/z分别选择173和315。考察确定最佳温孵条件，进行藁本内酯代谢的酶促反应动力学研究，通过特异性抑制试验，探讨参与藁本内酯代谢的主要同工酶。结果显示，酮康唑、甲氧苄啶、α-萘黄酮显著抑制藁本内酯的体外代谢，而奥美拉唑、4-甲基吡唑、奎尼丁对其体外代谢影响不大。可见CYP3A4、CYP2C9和CYP1A2是参与藁本内酯代谢的主要代谢酶，CYP2C19、CYP2E1和CYP2D6没有明显参与催化其代谢。

Enzyme kinetics of ligustilide metabolism in rat liver microsomes

To study the enzyme kinetics of ligustilide metabolism and the effects of selective CYP450    inhibitors on the metabolism of ligustilide in liver microsomes of rat, a LC-MS method was established for  quantitative analysis of ligustilide in liver microsomes incubation system with nitrendipine as internal standard.  The determination m/z for ligustilide was 173, and for nitrendipine, 315.  An optimum incubation system was found and various selective CYP inhibitors were used to investigate their inhibitory effects on the metabolism of ligustilide.  The results showed that enzyme kinetics of ligustilide could be significantly inhibited by ketoconazole, trimethoprim and α-naphthoflavon but scarcely inhibited by omeprazole, 4-methylpyrazole and quinidine.  Therefore, CYP3A4, CYP2C9 and CYP1A2 are the major isoenzyme participated in in vitro metabolism of ligustilide.