| 郑造乾,骆瑾瑜,陈燕华,王小军.探针药物法评价苦碟子注射液对大鼠肝微粒体CYP3A4的体外抑制作用[J].浙江中西医结合杂志,2017,27(2): |
| 探针药物法评价苦碟子注射液对大鼠肝微粒体CYP3A4的体外抑制作用 |
| In vitro inhibition of Kudiezi injection on rat liver microsomal CYP3A4 using probe drug |
| 投稿时间：2016-09-01 修订日期：2016-12-07 |
| DOI： |
| 中文关键词: 苦碟子注射液 鼠肝微粒体 细胞色素P450 3A 抑制作用 中药-西药相互作用 |
| 英文关键词:Ixeris sonchifolia injection rat liver microsomes cytochrome P450 3A4 inhibitory effect Herb–drug interaction |
| 基金项目:浙江省中医药科学研究基金计划（2013ZB012） |
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| 中文摘要: |
| 摘 要 目的 考察苦碟子注射液对大鼠肝微粒体CYP3A4的体外抑制作用，以预测苦碟子注射液与CYP 3A4酶底物合用药时可能产生的相互作用，确保临床用药的安全性和有效性。方法 采用SD大鼠肝微粒体体外孵育法，设阴性对照组、阳性抑制剂对照组和苦碟子注射液组。利用高效液相色谱法测定底物睾酮的减少量，计算得到IC50, 评价苦碟子注射液对大鼠肝微粒体CYP 3A4酶的抑制活性，以酮康唑用作阳性对照药。结果 在体外人肝微粒体孵育体系中，当Tris-HCl 缓冲液浓度为0.1 mol?L-1，pH为7.4，温度为37 ℃时，睾酮最佳反应底物浓度为100 μmol?L?1，最佳孵育时间为40 min，最佳蛋白浓度为0.5 mg?mL?1。结果显示，阳性抑制剂酮康唑的IC50 值为0.0707 μmol?L-1，表明孵育体系满足CYP 3A4酶抑制活性的评价要求。8 个不同体积终浓度（0.00%, 0. 01%, 0. 10%, 0. 20%, 0. 50%, 1. 00%, 2. 00%, 5. 00%, 10. 00%）的苦碟子注射液对CYP 3A4酶的相对抑制率分别为0.00%, 2.94%, 16.44%, 22.70%, 31.44%, 37.47%, 46.37%, 51.74%和60.40%，半数抑制率IC50 值为3.46%，高于其日用药量浓度。结论 在体外，正常剂量下，苦碟子注射液对人CYP 3A4无明显抑制作用，可以与其底物联合用药。 |
| 英文摘要: |
| ABSTRACT Objective To explore the potential herb-drug interaction between Kudiezi injection(KDZi) and drugs metabolized by CYP 3A4 enzyme in clinical application, the activity of CYP 3A4 affected by KDZi was detected using probe drug method in rat liver microsomes. Methods The test groups included a negative control group, an inhibitor positive control group and an KDZi group. After incubating the rat liver microsomes with a testosterone of probe drug, the reduction of testosterone were quantitated with HPLC, and IC50 values were calculated to assess the inhibitory effect of KDZi on rat CYP 3A4 enzyme. Ketoconazole was used as a positive control. Results In mixture metabolic system of liver microsome enzymes, the most suitable incubation concentration of testosterone was 100 μmol?L?1, incubation time was 40 min and concentration of microsome protein was 0.5 mg?mL?1, when the concentration of Tris - HCl buffer was 0.1 mol?L-1 (pH 7.4) at 37 ℃. The results showed that the IC50 value of positive inhibitors of CYP 3A4 was 0.0707 μmol?L-1, which indicated that the incubation system incubation system could satisfy the demands of CYP 3A4 enzyme inhibition activity evaluation. The relative inhibitory rate of CYP 3A4 in 8 serial volume concentration of KDZi（0.00%, 0. 01%, 0. 10%, 0. 20%, 0. 50%, 1. 00%, 2. 00%, 5. 00%, 10. 00%） were 0.00%, 2.94%, 16.44%, 22.70%, 31.44%, 37.47%, 46.37%, 51.74%, and 60.40%, respectively. The IC50 value of KDZi on CYP 3A4 inhibition was 3.46% which was exceeded their daily-dose concentration. Conclusion Under ordinary condition, no significant interaction between KDZi and CYP3A4 is detected in vitro, which indicates that KDZi might be used with CYP 3A4 enzyme substrates. |
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