中国临床药理学杂志2017，Vol.33Issue(21)：2150-2153,4.DOI:10.13699/j.cnki.1001-6821.2017.21.017
斑蝥酸钠维生素B6和复方苦参注射液对人肝微粒体细胞色素P450酶活性的抑制作用
Inhibitory effects of compound sophora and disodium cantharidinate and vitamin B6 injections on the activity of cytochrome P450 enzymes in human liver microsomes
摘要
Abstract
Objective To evaluate the inhibitive effects of disodium cantharidinate and vitamin B6 and compound sophora injections on 7 main cytochrome P450 (CYP450) isoforms in human microsomes in vitro for predicting the drug-drug interactions in clinical application.Methods Different concentrations of test disodium cantharidinate and vitamin B6 and compound sophora injections were incubated with human microsomes.phenacetin,bupropion,amodiaquine,(S)-mephenytoin,dextromethorphan,midazolam,testosterone were used as the substrates of CYP1A2,CYP2C9,CYP2C19,CYP2D6,CYP3A4-M,2B6,2C8 and CYP3A4-T,respectively.After the co-incubation,the metabolite of each substrate was analyzed by LC-MS/MS assay and then hemi-inhibitory concentration (IC50) was calculated.Results IC50 values(＞ 10 mg) of disodium cantharidinate and vitamin B6 were totally exceed its daily-dose (0.1-0.5 mg).IC50 values of compound sophora injection on CYP1A2,2D6,2C8,2C19 were 15.2,10.3,21.1 and 21.1 mL,respectively,which were less than or near to its daily-dosage.However,compound sophora injection's IC50 values on CYP2B6,2C9,3A4-M and 3A4-T were 63.5,72.0,95.5,92.5mL,which were much higher than its daily-dosage (20 mL).Conclusion Disodium Cantharidinate and vitamin B6 showed no inhibition on 7 main CYP450 isoforms in vitro at clinical normal dosage,while the inhibitory effects of compound sophora injection on the activities of CYP1A2,2D6,2C8,2C19 were strong and medium,respectively,but without inhibitory effect on the activities of other P450 isoforms.So,drug-drug interaction induced by inhibition of CYP450 enzymes should be paid more attention when compound sophora injection is used intravenously for therapy.关键词
斑蝥酸钠维生素B6/复方苦参/细胞色素P450酶/酶抑制/药物相互作用/肝微粒体Key words
disodium cantharidinate and vitamin B6 Injection/compound sophora/cytochrome P450 enzyme/enzyme inhibition/drug interaction/liver microsome分类
医药卫生引用本文复制引用
蔡小军,黄凯,宋惠珠,温浩,洪远..斑蝥酸钠维生素B6和复方苦参注射液对人肝微粒体细胞色素P450酶活性的抑制作用[J].中国临床药理学杂志,2017,33(21):2150-2153,4.基金项目
江苏省药学会医院药学基金资助项目(201409) （201409）
