重组细胞色素P4503A4和P4503A22细胞微粒体药物代谢动力学比较研究  

A Comparison of Pharmacokinetics by Microsomes in the Recombinant Cell Lines HepG2-P4503A4 and HepG2-P4503A22

作　　者：薛正楷[1,2] 魏泓[2] 

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

出　　处：《西南师范大学学报（自然科学版）》2014年第4期102-109,共8页Journal of Southwest China Normal University(Natural Science Edition)

基　　金：国家"十五"科技攻关计划重点项目资助课题(2004BA717B23)

摘　　要：目的:利用已建立的巴马小型猪细胞色素P4503A22和P4503A4稳定表达重组肝癌细胞株微粒体,分析比较二者的药物代谢动力学特征.方法: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,将探针药物与重组P4503A4,P4503A22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,通过高效液相色谱仪检测其药物代谢(抑制)动力学参数,并将二者进行比较分析.结果:P4503A22的硝苯地平、睾酮的代谢活性均低于P4503A4(p<0.05);酮康唑对P4503A4和P4503A22的硝苯地平代谢具有较强的抑制活性,但酮康唑对P4503A4的抑制活性强于P4503A22(p<0.05).结论:无论是代谢底物或抑制底物活性,重组P4503A22细胞微粒体活性均低于重组P4503A4细胞微粒体活性.Obj ective:To compare the pharmacokinetic characteristics of two microsomes prepared from the recombinant cell lines cytochrome P4503A22 and cytochrome P4503A4.Methods:NF (nifedipine)and TST (testosterone),which are the substrates of the specific metabolism of P4503A,and their inhibitor KCZ (ketoconazole)were used as the probe drugs and incubated in vitro with the microsomes prepared from the recombinant cell lines HepG2-P4503A4 and HepG2-P4503A22 under optimal conditions (micro-some concentration,drug concentration and incubation time).HPLC (high performance liquid chromatog-raphy)was utilized to detect the metabolites after incubation,and the pharmacokinetic characteristics were analyzed based on the experimental data.Results:The metabolic activities of cytochrome P4503A22 to both nifedipine and testosterone were lower than those of cytochrome P4503A4 (p<0.05).Ketoconazole showed a strong inhibitory activity to both cytochromes,but the inhibitory activity to P4503A4 was stron-ger than that to P4503A22 (p<0.05).Conclusion:P4503A4 has a stronger substrate metabolic activity and inhibitory activity than P4503A22.

关 键 词：重组细胞 微粒体 细胞色素P4503A4 细胞色素P4503A22 药物代谢 

分 类 号：R969.1[医药卫生—药理学]