重组细胞色素P4503A4与P4503A39微粒体药物代谢活性比较研究  

Comparison of Metabolic Activities Between Microsomes from Recombinant Cell Lines Human P4503A4 and S.scrofa P4503A39

作　　者：薛正楷[1,2] 魏弘[2] 

机构地区：[1]泸州职业技术学院生物医学工程研究所,四川泸州646005 [2]第三军医大学实验动物中心,重庆400038

出　　处：《亚太传统医药》2014年第5期9-13,共5页Asia-Pacific Traditional Medicine

基　　金：国家"十五"科技攻关计划重点项目(2004BA717B23)

摘　　要：目的:通过考察已建立的P4503A39和P4503A4稳定表达重组细胞株微粒体药物代谢动力学特征,旨在分子水平为巴马小型猪作为临床药物代谢试验动物提供科学依据。方法:制备重组细胞微粒体,以P4503A特异性代谢底物硝苯地平(NF)、睾酮及其抑制剂酮康唑(KCZ)为探针药物,将其与重组P4503A4、P4503A39细胞微粒体在优化的微粒体浓度、药物浓度、孵育时间等条件下进行体外孵育,获得药物代谢(抑制)动力学参数,并将二者进行比较分析。结果:P4503A39和P4503A4体外微粒体药物代谢动力学参数Vmax、Km(S50)、Clint及IC50均表明:P4503A39的硝苯地平、睾酮的代谢活性及酮康唑的抑制活性均显著低于P4503A4(P<0.05)。结论:重组P4503A39细胞微粒体活性显著低于重组P4503A4细胞微粒体活性。Objective：the purpose of this study to provide evidence for Bama miniature pig as a preclinical model animal through the drug metabolic kinetics of Sus. scrofa cytochromeP4503A39 and human cytochromeP4503A4. Methods： the probe drugs nifedipine （NF）. testosterone（TST） and ketoeonazole （KCZ）were incubated with microsomes from the recombinant cell lines of HepG2- P4503A4 and HepG2-P4503A39 in optimal conditions, the high performance liquid chromatograph （HPLC）was utilized to detect the metabolites after the incubation ended,the statistical analyses of metabolic characteristics was done Based on the experimental data. Results：the activity analyses demonstrated that the drug metabolic activities of nifedipine, testosterone and ketoeonazole by human P4503A4 were all significantly higher than those of P4503A39 （P〈0.05）. Conchlsion：P4503A4 showed higher substrate metabol- ic activity and inhibitory activity than those of P4503A39.

关 键 词：重组细胞 微粒体 细胞色素P4503A4 细胞色素P4503A39 药物代谢 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]