4代甘草酸制剂对大鼠肝微粒体CYP3A酶活性影响的比较  

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

作　　者：赵燕燕[1,2] 王静[1] 刘丽艳[3] 谷聪玲 

机构地区：[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

出　　处：《河北大学学报（自然科学版）》2017年第1期31-38,共8页Journal of Hebei University(Natural Science Edition)

基　　金：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)

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.To analyze the effects of four generations of glycyrrhizin preparations on the activity of CYP3 Aenzymes of rat liver microsomes by HPLC,rat liver microsomes were incubated with various concentrations of glycyrrhizin preparations and testosterone in vitro.The effect of CYP3 Aactivity 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 CYP3 Ain vitro.The first and second generations of glycyrrhizin preparations have an obvious inducing effect on the enzymic activity of CYP3 Ain rats.On the contrary,the third and fourth generations of glycyrrhizin preparations have a marked inhibition effect on CYP3 Aenzymes.The influence of glycyrrhizin preparation on CYP3 Aenzymes 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.

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 

分 类 号：R917[医药卫生—药物分析学]