Effect of Compatibility of Xuefuzhuyu Decoction(血府逐瘀汤)on CYP450 Metabolic Enzyme in Rats
Objective To clarify the hidden dangers of concomitant medication of Xuefu Zhuyu Decoction(血府逐瘀汤,XFZY).To investigate the effects of Xuefu Zhuyu Decoction,blood-activating group[Taohong Siwu Decoction(桃红四物汤)]and Qi-regulating group[Sini Powder(四逆散)]on 5 enzyme subtypes cytochrome P450 enzyme 1A2(CYP1A2),cytochrome P450 enzyme 2C11(CYP2C11),cytochrome P450 enzyme 2D2(CYP2D2),cytochrome P450 enzyme 3A1/2(CYP3A1/2)and cytochrome P450 enzyme 2C6(CYP2C6).Methods Twenty-four SD rats were randomly divided into blank control group,Qi-regulating group,blood-activating group and compound group.After continuous intragastric administration for 14 days,the mixed probe drugs including caffeine(CAF),omeprazole(OMP),dextromethorphan(DM),midazolam(MDZ)and losartan potassium(LK)were given.The corresponding metabolites in rats were 1,7-dimethylxanthine(PXT),5-hydroxyomeprazole(HOMP),nordextromethorphan(DP),1-hydroxymidazolam(HMDZ)and carbonyl losartan(LC).Online SPE-LC-MS/MS was used to detect the plasma concentrations of probe drugs and specific metabolites at different time points.The pharmacokinetic parameters and metabolic rates of probe drugs and metabolites were compare and the effects of repeated administration of XFZY and its effi-cacy combination group on the activity of CYP450 enzyme in rats were evaluated.Results Repeated administration of XFZY and each efficacy combination group had no significant effect on the activities of CYP2C11 and CYP3A1/2 metabolic enzymes in rats.XFZY had no significant effect on the activity of CYP1A2 metabolic enzyme,while blood-activating group showed certain induc-tion effect on the activity of CYP1A2 metabolic enzyme(P＜0.05).XFZY had a significant inhibitory effect on CYP2D2(P＜0.01),and the inhibitory effect may come from blood-activating drugs.XFZY showed a tendency to induce CYP2C6 activity in rats,but there was no statistical significance.Conclusion Repeated administration of XFZY has a certain inhibitory effect on hu-man CYP2D6 in rats,which may be attributed to blood-activating drugs.XFZY has no significant effect on CYP1A2,CYP2C11,CYP3A1/2 or CYP2C6 enzyme activities in rats.It is suggested that XFZY should not be used in combination with drugs metabo-lized by CYP2D6.
万方数据
维普
