3种心血管类中药注射液对人肝微粒体CYP450酶的体外抑制作用  

Inhibition of 3 cardiovascular traditional Chinese medicine injections on human cytochrome P450 in vitro

作　　者：刘艳文[1] 刘黎[1] LIU Yan-wen;LIU Li(Department of Pharmacy,Hunan Brian Hospital/Second People’s Hospital of Hunan,Changsha 410007)

机构地区：[1]湖南省脑科医院/湖南省第二人民医院药学部,长沙410007

出　　处：《中南药学》2023年第1期7-13,共7页Central South Pharmacy

基　　金：湖南省自然科学基金项目(No.2020JJ9029);湖南省中医药科研计划项目(No.2021107)。

摘　　要：目的研究冠心宁注射液、心脉隆注射液和丹红注射液对人肝微粒体细胞色素P450(CYP450)酶3种亚型(CYP1A2、CYP2C19、CYP3A4)的体外抑制作用。方法3种中药注射液6个不同体积分数的工作液分别与CYP1A2、CYP2C19、CYP3A4对应的混合探针药物在人肝微粒体中共同孵育,采用超高效液相色谱-串联质谱(UPLC-MS/MS)法同时测定探针药物的代谢产物,即对乙酰氨基酚(CYP1A2)、5-羟基奥美拉唑(CYP2C19)、6β-羟基睾酮(CYP3A4)的生成量,计算半数抑制浓度(IC_(50))。结果在设定的浓度范围内,3种中药注射液对CYP1A2、CYP2C19、CYP3A4的抑制作用存在浓度依赖性;冠心宁注射液对CYP2C19、CYP3A4的IC_(50)分别为3.76%、9.87%;心脉隆注射液对CYP1A2、CYP2C19的IC_(50)分别为4.81%、2.65%;丹红注射液对CYP1A2、CYP2C19和CYP3A4的IC_(50)分别为16.74%、11.10%和9.84%。结论在临床使用剂量下,冠心宁注射液、心脉隆注射液和丹红注射液对CYP1A2、CYP2C19、CYP3A4有一定的抑制作用。Objective To determine the inhibitory effect of 3 cardiovascular traditional Chinese medicine injections(TCM injections)on 3 cytochrome P450(CYP450)enzymes(CYP1A2,CYP2C19,CYP3A4),in human liver microsomes in vitro.Methods Totally 3 cardiovascular TCM injections with 6 concentrations were incubated with human liver microsomes in the presence of CYP1A2,CYP2C19,CYP3A4.UPLC-MS/MS method was used to simultaneously determine the 3 probe substrate-derived metabolites,that was acetaminophen(CYP1A2),5-hydroxy omeprazole(CYP2C19)and 6β-hydroxytestosterone(CYP3A4).The half maximal inhibitory concentration(IC_(50))values were calculated.Results The 3 cardiovascular TCM injections showed concentrationdependent inhibition on CYP1A2,CYP2C19,CYP3A4 in the present concentration range.The IC_(50)of Guanxinning injection of CYP2C19 and CYP3A4 was 3.76%and 9.87%;the IC_(50) of Xinmailong injection of CYP1A2 and CYP2C19 was 4.81%and 2.65%;and the IC_(50) of Danhong injection of CYP1A2,CYP2C19 and CYP3A4 was 16.74%,11.10%and 9.84%respectively.Conclusion Guanxinning injection,Xinmailong injection and Danhong injection have inhibitory effect on CYP1A2,CYP2C19,CYP3A4 at the clinical dosage in vitro.

关 键 词：中药注射液 人肝微粒体 细胞色素P450 抑制作用 药物相互作用 

分 类 号：R965[医药卫生—药理学] R285[医药卫生—药学]