痹祺胶囊配伍组分对体内CYP450同工酶活性的影响

Effects of components in Biqi Capsulae prescription compatibility on activities of cytochrome P450 in vivo

目的通过体内实验评价痹祺胶囊配伍组方对细胞色素P450同工酶(cytochrome P450,CYP450)活性的影响。方法采用全新的"Cocktail"一点法,建立LC-MS/MS法测定大鼠体内5种探针药物非那西丁、甲苯磺丁脲、美芬妥英、右美沙芬和咪达唑仑及其相应的代谢产物的浓度,分析和评估痹祺胶囊配伍组分对大鼠体内5种CYP450酶的诱导和/或抑制作用。结果痹祺胶囊组方存在基于CYP450的配伍规律,与空白对照组比较,君药+臣药组、君药+使药组、君药+臣药+佐药组、君药+臣药+使药组、君药+佐药+使药组及痹祺胶囊全药组对CYP1A2具有显著诱导作用;君药+臣药组、君药+臣药+佐药组、君药+臣药+使药组及痹祺胶囊全药组对CYP2C9具有显著诱导作用。结论痹祺胶囊组方存在基于CYP450酶较显著的配伍规律,为进一步研究痹祺胶囊组方配伍的科学性和安全性奠定良好基础。

Objective To investigate and evaluate the effect of components in Biqi Capsulae prescription compatibility on activities of cytochrome P450 （CYP450） in vivo. Methods A new ＂Cocktail＂ one point method has been established, including five probes of Phenacetin, Tolbutamide, mephenytoin, Dextromethorphan, and midazolam. An LC-MS/MS analytical method has been established to determine the above five probes and their corresponding metabolites to analyze and evaluate the potential in vivo induction and （or） inhibition of components from Biqi Capsulae on the above five CYP450 in rats. Results Biqi Capsulae prescription has compatibility based on CYP450. Compared with blank group, groups of ＂principal ＋ assistant＂, ＂principal ＋ mediator＂, ＂principal ＋ assistant ＋ complement＂, ＂principal ＋ assistant ＋ mediator＂, ＂principal ＋ complement ＋ mediator＂, and whole Biqi Capsulae could significantly induce the activity of CYP1A2. Moreover, groups of ＂principal ＋ assistant＂, ＂principal ＋ assistant ＋ complement＂, ＂principal ＋ assistant ＋ mediator＂, and whole Biqi Capsulae could significantly induce the activity of CYP2C9. Conclusion Biqi Capsulae prescription has significant compatibility based on CYP450. These results provide the important information and establish good foundation for further investigation on scientificalness and safety of Biqi Capsulae prescription compatibility.