10种心血管类中药注射剂对人细胞色素P_(450)7种亚型的体外抑制作用  

Inhibitory Effect of 10 Kinds of Cardiovascular TCM Injections on 7 Subtypes of Human Cytochrome P_(450) in vitro

作　　者：刘丽雅[1,2] 韩永龙[2] 余奇[2] 朱金辉[2] 郭澄[1,2] 

机构地区：[1]上海中医药大学,上海201203 [2]上海交通大学附属第六人民医院药剂科,上海200233

出　　处：《中国药房》2014年第11期990-993,共4页China Pharmacy

基　　金：上海市卫生局中医药科研基金(No.2012L058A);上海市医院协会科研基金(No.201002029)

摘　　要：目的:研究10种心血管类中药注射剂对人细胞色素P450(CYP)7种亚型(CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A4/5)的体外抑制作用。方法:10种心血管类中药注射剂9个不同质量浓度的工作液分别与7种CYP亚型对应的混合探针药物在人肝微粒体中共同孵育,采用高效液相色谱-串联质谱(LC-MS/MS)法同时测定这7种探针药物的代谢产物,即对乙酰氨基酚(CYP1A2)、羟基安非他酮(CYP2B6)、去甲阿莫地喹(CYP2C8)、4-羟基双氯芬酸(CYP2C9)、4-羟基美芬妥英(CYP2C19)、右啡烷(CYP2D6)、1-羟基咪达唑仑(CYP3A4/5)的质量浓度,计算半数抑制浓度(IC50),并确定对CYP有抑制作用的中药注射剂。结果:CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A4/5的阳性抑制剂呋拉茶碱、塞替派、槲皮素、磺胺苯吡唑、噻氯匹定、奎尼丁和酮康唑对相应酶型均表现出明显抑制作用;10种心血管类中药注射剂中丹红注射液对CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C19、CYP2D6和CYP3A4/5均有明显抑制作用,红花注射液对CYP2C8有明显抑制作用。结论:在正常体积分数/质量浓度下,丹红注射液对人CYP 7种亚型在体外均有明显抑制作用;红花注射液对人CYP2C8在体外有明显抑制作用。OBJECTIVE： To study the inhibitory effects of 10 kinds of cardiovascular TCM injections on 7 subtypes of human cytochrome P450 （CYP1A2, CYP2B6, CYP2CS, CYP2C9, CYP2C19, CYP2D6 and CYP3A4/5）. METHODS： 10 kinds of cardiovascular TCM injections with 9 different concentrations were incubated with human liver microsomes in the presence of 7 probe substrates of CYP450 isoforms, respectively. LC-MS/MS method was used to simultaneously determine 7 probe substrate-derived metabolites, i.e. acetaminophen （CYP1A2） , hydroxy-bupropin （CYP2B6）, n-desethyl-amodiaquine （CYP2CS） , 4＇-hydroxy-dicl- ofenac （CYP2C9） , 4＇ -hydroxy-mephenytoin （CYP2C 19） , dextrorphan （CYP2D6） and 1-hydroxy-midazolam （CYP3A）.The half maximal inhibitory concentration （IC50） values were calcalated, and TCM injection which inhibited CYP was determined. RESULTS： Positive inhibitors of CYP1A2, CYP2B6, CYP2CS, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, i.e. furafylline, thiotepa, quercetin, sulfaphenazolum, ticlopidine, quinidine and ketoconazole significantly inhibited related enzyamtic types; among 10 kinds of cardiovascular TCM injections, Danhong injection significantly inhibited CYP1A2, CYP2B6, CYP2CS, CYP2C9, CYP2C19, CYP2D6 and CYP3A4/5; Honghua injection significantly inhibited CYP2C8. CONCLUSIONS： Danhong injection shows significant inhibitory effect on 17 subtypes of CYP in vitro; Honghua injection shows significant inhibitory effect on CYP2C8 under normal dosage.

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

分 类 号：R285[医药卫生—中药学] R97[医药卫生—中医学]