Comparative analysis of the effect of the four generations of glycyrrhizin preparations on rat liver microsomal CYP3A activity

doi:10.3969/j.issn.1000-1565.2017.01.006

摘要/Abstract

摘要： 对国内外上市的4代甘草酸制剂对肝微粒体CYP3A酶活性的影响进行分析与比较.将CYP3A酶的特异性探针睾酮和不同浓度的甘草酸制剂加入体外大鼠肝微粒体孵育体系,用高效液相色谱法测定睾酮的羟基化代谢产物6β-羟基睾酮的含量,评价甘草酸制剂对大鼠肝微粒体CYP3A酶活性的影响.结果显示,所采用的方法符合生物样品检测标准;上市4代甘草酸制剂对CYP3A酶表现出诱导或抑制作用,第1、2代甘草酸制剂对CYP3A酶活性的影响以诱导作用为主,第3、4代甘草酸制剂对CYP3A酶活性的影响以抑制作用为主.每种甘草酸制剂对CYP3A酶活性强度的影响与给药浓度有关,结果有显著性差异.联合用药时应考虑不同甘草酸制剂对CYP3A酶活性的影响,研究结果为临床合用药物相互作用的研究以及剂量的调整提供依据.

关键词: 4代甘草酸制剂, 高效液相色谱法, CYP3A酶, 相对活性, 比较分析

Abstract: To analyze the effects of four generations of glycyrrhizin preparations on the activity of CYP3A enzymes of rat liver microsomes by HPLC,rat liver microsomes were incubated with various concentrations of glycyrrhizin preparations and testosterone in vitro.The effect of CYP3A activity of glycyrrhizin preparations was evaluated by the amount of 6β-hydroxy testosterone which was determined by HPLC.The result illustrated that this method met the standard for biological sample.The glycyrrhizin preparations could induce or inhibit the enzyme activity of rat liver CYP3A in vitro.The first and second generations of glycyrrhizin preparations have an obvious inducing effect on the enzymic activity of CYP3A in rats.On the contrary,the third and fourth generations of glycyrrhizin preparations have a marked inhibition- DOI:10.3969/j.issn.1000-1565.2017.01.0064代甘草酸制剂对大鼠肝微粒体CYP3A酶活性影响的比较赵燕燕^1,2,王静¹,刘丽艳³,谷聪玲²(1.河北大学化学与环境科学学院,河北保定 071002;2.河北大学药学院河北省药物质量分析控制重点实验室,河北保定 071002;3.河北大学医学综合实验中心,河北保定 071000)摘要:对国内外上市的4代甘草酸制剂对肝微粒体CYP3A酶活性的影响进行分析与比较.将CYP3A酶的特异性探针睾酮和不同浓度的甘草酸制剂加入体外大鼠肝微粒体孵育体系,用高效液相色谱法测定睾酮的羟基化代谢产物6β-羟基睾酮的含量,评价甘草酸制剂对大鼠肝微粒体CYP3A酶活性的影响.结果显示,所采用的方法符合生物样品检测标准;上市4代甘草酸制剂对CYP3A酶表现出诱导或抑制作用,第1、2代甘草酸制剂对CYP3A酶活性的影响以诱导作用为主,第3、4代甘草酸制剂对CYP3A酶活性的影响以抑制作用为主.每种甘草酸制剂对CYP3A酶活性强度的影响与给药浓度有关,结果有显著性差异.联合用药时应考虑不同甘草酸制剂对CYP3A酶活性的影响,研究结果为临床合用药物相互作用的研究以及剂量的调整提供依据.关键词:4代甘草酸制剂;高效液相色谱法;CYP3A酶;相对活性;比较分析中图分类号:R917 文献标志码:A 文章编号:1000-1565(2017)01-0031-08Comparative analysis of the effect of the four generations of glycyrrhizinpreparations on rat liver microsomal CYP3A activityZHAO Yanyan^1,2,WANG Jing¹,LIU Liyan³,GU Congling²(1.College of Chemistry and Environmental Science,Hebei University,Baoding 071002,China;2.Key Laboratory of Pharmaceutical Quality Control of Heibei Province,College of PharmaceuticalSciences,Hebei University,Baoding 071002,China; 3.Experimental Center of Medicine,Hebei University,Baoding 071000,China)Abstract: To analyze the effects of four generations of glycyrrhizin preparations on the activity of CYP3A enzymes of rat liver microsomes by HPLC,rat liver microsomes were incubated with various concentrations of glycyrrhizin preparations and testosterone in vitro.The effect of CYP3A activity of glycyrrhizin preparations was evaluated by the amount of 6β-hydroxy testosterone which was determined by HPLC.The result illustrated that this method met the standard for biological sample.The glycyrrhizin preparations could induce or inhibit the enzyme activity of rat liver CYP3A in vitro.The first and second generations of glycyrrhizin preparations have an obvious inducing effect on the enzymic activity of CYP3A in rats.On the contrary,the third and fourth generations of glycyrrhizin preparations have a marked inhibition- 收稿日期:2016-04-20 基金项目:河北省自然科学基金资助项目(H2013201203);河北大学医学学科专项资金建设资助项目(2014A1003) 第一作者:赵燕燕(1960—),女,天津人,河北大学教授,主要从事药学以及将现代分离技术用于临床、药学、食品、环境等方面的研究工作.E-mail:zhaoyany606@126.com第1期赵燕燕等:4代甘草酸制剂对大鼠肝微粒体CYP3A酶活性影响的比较 effect on CYP3A enzymes.The influence of glycyrrhizin preparation on CYP3A enzymes activity varies with the concentration.The research in this paper indicates that it is importance to select a reasonable glycyrrhizin preparation in case of drug interation.The result of this paper can provide reference for the research of clinical co-administrated drugs and dose adjustment.

Key words: four generations of glycyrrhizin preparations, HPLC, CYP3A, relative activity, comparative analysis

中图分类号:

R917

赵燕燕,王静,刘丽艳,谷聪玲. [J]. 河北大学学报(自然科学版), 2017, 37(1): 31-38.

ZHAO Yanyan,WANG Jing,LIU Liyan,GU Congling. Comparative analysis of the effect of the four generations of glycyrrhizin preparations on rat liver microsomal CYP3A activity[J]. Journal of Hebei University (Natural Science Edition), 2017, 37(1): 31-38.

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