器官移植受者外周血单个核细胞中免疫抑制剂药物浓度的影响因素研究进展  

Research advances on influencing factors of immunosuppressant concentration in peripheral blood mononuclear cell of organ transplant recipients

作　　者：郭朋朋 刘亚妮[1] 师少军[1] 张蕊 GUO Peng-peng;LIU Ya-ni;SHI Shao-jun;ZHANG Rui(Department of Pharmacy,Affiliated Union Hospital,Tongji Medical College,Huazhong University of Science&Technology,Hubei Wuhan 430022,China)

机构地区：[1]华中科技大学同济医学院附属协和医院药学部,湖北武汉430022

出　　处：《中国医院药学杂志》2021年第8期855-859,共5页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金面上项目(编号:81874326);吴阶平医学基金会临床科研专项资助基金(320.6750.19090-43);湖北省卫健委中医药科研项目(重点项目)(编号:ZY2019Z004);国家重点研发计划资助(编号:2017YFC0909900)。

摘　　要：随着实体器官移植技术的发展与免疫抑制剂的应用,免疫抑制剂的常规血药浓度检测已经不能满足临床现实要求。出现了患者血药浓度在治疗窗内,但仍然发生了急性排斥反应等临床不良事件的现象。淋巴细胞是免疫抑制剂作用的靶细胞,越来越多的研究也证实外周血单个核细胞(peripheral blood mononuclear cells, PBMCs)内药物浓度比全血药物浓度更能准确反映药物在体内的药物效应。然而影响PBMCs内药物浓度的因素尚不明确,本文在对现有的研究进行查阅并总结后,得到了目前已知的影响因素包括代谢酶、药物转运体基因多态性,以及性别、年龄等其他因素引起的代谢酶和转运体的活性改变从而引起细胞内药物浓度的变化。本综述对代谢酶以及转运体对PBMCs内药物浓度的影响因素以及其相关作用机制展开讨论。With the continuous development of solid organ transplantation technology and the widespread applications of immunosuppressants(IS),the routine detection of blood concentration of immunosuppressants can no longer meet the requirements of clinical practices.Some patient’s blood concentration fell within the therapeutic window.However, acute rejection persisted.Immunosuppressants target lymphocytes, and many studies have confirmed that drug concentration in peripheral blood mononuclear cells(PBMCs)can exactly reflect the drug effect than whole blood drug concentration.However, the influencing factors of drug concentration in peripheral blood mononuclear cells have remained unclear.After reviewing and summarizing current studies, the known influencing factors including gene polymorphisms of metabolic enzymes and drug transporter.And changes in the activities of metabolic enzymes and transporters caused by gender, age and other factors may result in intracellular drug concentration.This review discussed the influencing factors of metabolic enzymes and transporters in the concentration of drugs in peripheral blood mononuclear cells and their related acting mechanisms.

关 键 词：代谢酶 转运体 外周血单个核细胞 

分 类 号：R969[医药卫生—药理学]