Effects of Shuangshen Ningxin Capsules and its compatible components on cytochrome P450 enzymes in rats
Objective:In order to prevent potential danger of clinical combination drug caused by drug interaction,we initially pursued the effects of traditional Chinese medicine compound Shuangshen Ningxin Capsules and its components on CYP450s in rats.Methods:The rats were randomly divided into the blank control group,Salviae Miltiorrhizae Radix et Rhizoma group,Ginseng Radix et Rhizoma group,Corydalis Rhizoma group,and SSNX group.The rats were orally administrated with the mixed probe drugs including caffeine,losartan,omeprazole,dextromethorphan and midazolam for consecutive 14 days,five CYP450s enzyme subtypes CYP1A2,CYP2C6,CYP2C11,CYP2D2 and CYP3A1/2 in rats were detected respectively.The blood concentrations of each probe drug and its specific metabolites at different time points were detected.To compare the changes of pharmacokinetic parameters and metabolic rate in probe drugs and the metabolites,and evaluate the effect of repeated administration of Shuangshen Ningxin Capsules on the activities of CYP450s in rats.Results:Compared with the blank control group,there was no statistically significant change in the in vivo metabolic rates of each probe drug after repeated administration of Shuangshen Ningxin Capsules,so there was no significant effect on the activities of five metabolic enzymes in rats.However,it significantly delayed the Tmax of PXT(P＜0.05),and the T1/2 of omeprazole(P＜0.05).It also increased especially the Cmax and AUC of the metabolite of dextromethorphan(P＜0.05,P＜0.01),which was consistent with the trend after the administration of Ginseng Radix et Rhizoma and Corydalis Rhizoma.After administration of Ginseng Radix et Rhizoma and Corydalis Rhizoma,the Cmax and AUC of losartan and its metabolites were increased(P＜0.05,P＜0.01).Conclusion:Repeated administration of compound Shuangshen Ningxin Capsules did not induce or inhibit significantly the enzyme activities of CYP1A2,CYP2C6,CYP2C11,CYP2D2 and CYP3A1/2 in rats,and it was the comprehensive result of the effects of each single group of prescriptions on metabolic enzymes,preliminarily indicating that the clinical application of Shuangshen Ningxin Capsules was less likely to cause adverse reactions due to drug interaction.
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