中药复方双参宁心胶囊及其配伍组分对大鼠细胞色素P450酶的影响  

Effects of Shuangshen Ningxin Capsules and its compatible components on cytochrome P450 enzymes in rats

作　　者：苗兰[1] 彭勍[1] 张颖[1] 孙明谦[1] 任常英 林晓斐 刘建勋[1] 林力[1] MIAO Lan;PENG Qing;ZHANG Ying;SUN Mingqian;REN Changying;LIN Xiaofei;LIU Jianxun;LIN Li(Institute of Basic Medical Sciences of Xiyuan Hospital of CACMS,Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine,Beijing 100091,China)

机构地区：[1]中国中医科学院西苑医院,基础医学研究所,中药药理北京市重点实验室,北京100091

出　　处：《中华中医药杂志》2024年第1期125-133,共9页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：中国中医科学院科技创新工程重大攻关项目(No.CI2021A05022,No.CI2021A04508);国家自然科学基金项目(No.81872992)。

摘　　要：目的:为预防药物相互作用可能导致的临床合并用药隐患,初步探讨中药复方双参宁心胶囊及其组方药物对大鼠细胞色素P450酶的影响。方法:30只大鼠随机分为空白对照组、丹参组、人参组、延胡索组及双参宁心组,每组6只,连续灌胃14d,给予大鼠混合探针药:咖啡因、氯沙坦、奥美拉唑、右美沙芬和咪达唑仑,分别对应大鼠体内5种CYP450s酶亚型CYP1A2、CYP2C6、CYP2C11、CYP2D2和CYP3A1/2。检测探针药及特异代谢物不同时间点的血药浓度,比较探针药及代谢物的药代参数及代谢率的变化,评价重复给予双参宁心胶囊对大鼠CYP450酶活性的影响。结果:与空白对照组比较,双参宁心胶囊和各组方药对5种探针药的体内代谢率均没有显著性影响。同时双参宁心组咖啡因代谢物PXT达峰时间显著推迟(P<0.05),奥美拉唑的末端消除半衰期显著延后(P<0.05),右美沙芬代谢物的峰浓度和AUC值显著增加(P<0.05,P<0.01),这与人参和延胡索给药后趋势较一致;丹参组和延胡索组咖啡因表观分布容积均显著升高(P<0.01,P<0.05);人参和延胡索组氯沙坦及其代谢物的峰浓度和AUC值均升高(P<0.05,P<0.01)。结论:重复给予复方双参宁心胶囊对大鼠体内CYP1A2、CYP2C6、CYP2C11、CYP2D2和CYP3A1/2酶活性不存在显著诱导或抑制作用,是3个组方药对代谢酶作用的综合结果,初步提示临床上应用双参宁心胶囊出现药物相互作用引起不良反应的可能性较小。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 o

关 键 词：双参宁心胶囊 CYP450s 混合探针药物 代谢活性 药代动力学 

分 类 号：R285.5[医药卫生—中药学]