| 引用本文: | 何文娟,董维冲,赵晓娟,赵永红,刘秀菊,孙倩,王淑梅.细胞色素P450介导的氯沙坦钾对瑞格列奈在大鼠肝微粒体中代谢的影响[J].中国现代应用药学,2021,38(13):1577-1581. |
| HE Wenjuan,DONG Weichong,ZHAO Xiaojuan,ZHAO Yonghong,LIU Xiuju,SUN Qian,WANG Shumei.Effect of Losartan on the Metabolism of Repaglinide in Liver Microsomes of Rats by CYP450[J].Chin J Mod Appl Pharm(中国现代应用药学),2021,38(13):1577-1581. |
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| 摘要: |
| 目的 研究瑞格列奈在大鼠肝微粒体中的酶促反应动力学，并考察氯沙坦钾对其在大鼠肝微粒体中代谢的影响。方法 建立大鼠肝微粒体体外孵育体系对瑞格列奈的代谢进行研究；以洛伐他汀为内标，应用UPLC测定大鼠肝微粒体中瑞格列奈的浓度。采用底物减少法，通过GraphPad Prism 5.0软件计算瑞格列奈的酶促反应动力学常数Vmax和Km；分别以系列浓度氯沙坦钾（2.5~50μmol·L-1）与瑞格列奈（44 μmol·L-1）于37℃水浴中共同孵育，并测定肝微粒体中瑞格列奈的减少量，考察氯沙坦钾对瑞格列奈的抑制作用。结果 瑞格列奈在大鼠肝微粒体的最佳孵育时间为40 min，最佳蛋白质量浓度为1 mg·mL-1；瑞格列奈酶促反应动力学参数Vmax=47.29μmol·min-1·（mg·protein）-1，Km=51.41 μmol·L-1；氯沙坦钾对瑞格列奈在体外肝微粒体抑制作用的IC50值为17.89 μmol·L-1。结论 氯沙坦钾对瑞格列奈在大鼠肝微粒体中的代谢具有较强的抑制作用，两药联合应用可能发生相互作用，具有诱发低血糖的风险。 |
| 关键词: 瑞格列奈 氯沙坦钾 肝微粒体 UPLC 酶促反应动力学 IC50值 |
| DOI：10.13748/j.cnki.issn1007-7693.2021.13.007 |
| 分类号:R965.1 |
| 基金项目:河北省医学科学研究重点课题（20170572） |
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| Effect of Losartan on the Metabolism of Repaglinide in Liver Microsomes of Rats by CYP450 |
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HE Wenjuan, DONG Weichong, ZHAO Xiaojuan, ZHAO Yonghong, LIU Xiuju, SUN Qian, WANG Shumei
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Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
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| Abstract: |
| OBJECTIVE To characterize the enzymatic kinetics of repaglinide in rat liver microsome and study the effect of losartan on the metabolism of rat liver microsome. METHODS The metabolism of raglenay by establishing the in vitro incubation system of liver microsome in rats. UPLC method was used to detect the concentration of repaglinide in rat liver microsome with lovastatin as internal standard. The enzyme kinetic parameters of Vmax and Kmwas calculated by determining the reduction of repaglinide with GraphPad Prism 5.0 software. Repaglinide(44 μmol·L-1) was jointly incubated with a series of concentrations of losartan(2.5-50 μmol·L-1) in a 37℃ water bath, respectively. The reduction of repaglinide in liver microsomes was also measured, and the inhibitory effect of losartan potassium on repaglinide was investigated. RESULTS The optimal incubation time in rat liver microsomes was 40 min, and the optimal protein concentration was 1 mg·mL-1. The enzyme kinetics parameters of repaglinide were as follows:Vmax=47.29 μmol·min-1·(mg·protein)-1, Km=51.41 μmol·L-1. The IC50 value of the inhibitory effect of losartan potassium on repaglinide liver microsomes in vitro was 17.89 μmol·L-1. CONCLUSION Losartan has a significant effect on the metabolism of repaglinide in liver microsomes. Drug interaction may occur when the two drugs are combined, and there is a risk of hypoglycemia. |
| Key words: repaglinide losartan liver microsome UPLC enzyme kinetic IC50 value |
