CYP3A5基因多态性的他克莫司个体化用药临床研究分析  

Clinical therapy analysis of individualized medication of tacrolimus based on CYP3A5 gene polymorphism

作　　者：张恩瑶 向倩[1] 谢秋芬[1] 胡琨[1] 赵侠[1] 周颖[1,3] 崔一民[1,2,3] ZHANG En-yao;XIANG Qian;XIE Qiu-fen;HU Kun;ZHAO Xia;ZHOU Ying;CUI Yi-min(Department of Pharmacy,Peking University First Hospital,Beijing 100034,China;Institute of Clinical Pharmacology,Peking University First Hospital,Beijing 100034,China;Department of Pharmacy Administration and Clinical Pharmacy,School of Pharmaceutical Sciences,Peking University Health Science Center,Beijing 100191,China)

机构地区：[1]北京大学第一医院药学部,北京100034 [2]北京大学第一医院临床药理研究所,北京100034 [3]北京大学药学院药事管理与临床药学系,北京100191

出　　处：《中国临床药理学杂志》2022年第8期864-868,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81872940、82073935和81973395);国家重大新药创制基金资助项目(2017ZX09101001);北京市科学技术委员会医药创新品种研发培育及产业支撑平台能力建设基金资助项目(Z191100007619038)。

摘　　要：CYP3A5家族基因在肝含量占CYP3A总量一半以上,是许多药物代谢的酶。常见的免疫抑制药他克莫司是一种选择性抑制钙调磷酸酶,主要用于器官移植患者的抗排异治疗,经CYP3A5同工酶进行代谢。CYP3A5基因突变使酶失活,导致他克莫司不能正常代谢而在体内积聚,产生相关药物不良反应。由于产生充分免疫抑制效果的水平和产生毒性的水平差距很小,他克莫司使用时需要进行治疗药物监测,但是他克莫司的目标浓度因治疗的疾病而异,且操作复杂,初始用药剂量难以准确判定,给临床合理用药带来了困扰。基因型检测可以辅助指导他克莫司个体化治疗,在最大程度保证药物疗效的同时避免药物不良反应的发生。本研究综述了基于CYP3A5基因多态性的他克莫司个体化药物治疗现状,为抗排异治疗策略的优化提供参考。CYP3A enzymes account for 50%of the total P450 in an average human liver,and these enzymes participate in the metabolism of up to 50%of the drugs currently in use.Tacrolimus is a calcineurin inhibitor used to prevent organ transplant rejection and to treat moderate to severe atopic dermatitis.Tacrolimus inhibits calcineurin,which is involved in the production of interleukin-2,a molecule that promotes the development and proliferation of T cells,as part of the body’s learned(or adaptive)immune response.CYP3A5 gene polymorphism played an important role on the metabolic activation of tacrolimus.Gene sequences encoding drug-metabolizing enzymes CYP3A5 are an important cause of individualized differences in tacrolimus effects.Clinical genotyping tests can be used to examine the presence of the CYP3A5 mutant allele,predict the metabolic phenotype,and may help clinicians to adjust the use of immunosuppressant-inhibitor.This article reviewed the progress of individualized drug therapy of tacrolimus based on CYP3A5 gene polymorphism.Relevant guidelines were sorted out to provide reference for the optimization of therapy strategies for inhibition and immunity.

关 键 词：细胞色素P4503A5 他克莫司 个体化治疗 

分 类 号：R97[医药卫生—药品]