CYP3A5和MDR1基因型对尿毒症患者肾移植术后早期他克莫司血药浓度和肌酐水平的影响  

Effect of CYP3A5 and MDR1 gene polymorphism on blood concentration of tacrolimus and creatinine level in uremic patients during the early phase of kidney transplantation

作　　者：温燕 朱德康 傅尚希 邓易 张凤 陈万生 无 WEN Yan;ZHU Dekang;FU Shangxi;DENG Yi;ZHANG Feng;CHEN Wansheng;无(Department of Pharmacy,Second affiliated Hospital,Naval Medical University of the PLA,Shanghai 200003;Department of Academic Administrative Affairs,Naval Medical University of the PLA,Shanghai 200433,China;Department of Organ Transplantation,Naval Medical University of the PLA,Shanghai 200003,China)

机构地区：[1]海军军医大学第二附属医院药剂科,上海200003 [2]海军军医大学教务处,上海200433 [3]海军军医大学第二附属医院器官移植科,上海200003

出　　处：《药学实践杂志》2022年第2期165-170,共6页Journal of Pharmaceutical Practice

基　　金：院创新型临床研究资助(2020YLCYJ-Y25);上海市临床药学重点专科建设项目(2016-40044-002);上海市卫生计生系统重要薄弱学科建设项目(2016ZB0303);上海市“医苑新星”青年医学人才资助(2020临床药师项目);国家自然科学基金(81573793)。

摘　　要：目的评价真实临床实践中CYP3A5(CYP3A5*3,6986A>G)及MDR1(C3435>T,G2677>T/A,C1236>T)基因多态性对尿毒症患者接受肾移植术后早期他克莫司血药浓度的影响及其最佳治疗浓度。方法以入选2013~2017年单中心的131例首次肾移植术且术后以他克莫司为基础进行三联免疫治疗的患者为对象,开展回顾性研究,考察患者基因多态性对他克莫司的日剂量、血药浓度、血药浓度/剂量比值和肌酐水平的影响。结果在维持他克莫司靶浓度(10~15 ng/ml)的前提下,肾移植术后4周内基因型为CYP3A5*3/*3(GG)肾移植受者的给药剂量低于基因型CYP3A5*1/*1(AA)和CYP3A5*1/*3(AG)。患者血药浓度在10~13 ng/ml内时,其血肌酐水平最接近正常值。结论CYP3A5基因多态性影响肾移植受者他克莫司的血药浓度,未发现MDR1基因多态性对他克莫司血药浓度的影响。早期肾移植血药浓度控制在10~13 ng/ml时,患者移植肾功能最接近正常人肾功能水平。Objective To investigate the effect of CYP3A5 and MDR1 gene polymorphisms on blood concentration of tacrolimus and creatinine level in uremic patients during the early phase after kidney transplantation in real clinical practice.Methods 131 patients who underwent kidney transplantation for the first time with triple immunotherapy based on tacrolimus in single-center from 2013 to 2017 were enrolled for retrospective study.Tacrolimus daily dose,blood concentration,blood concentration-to-dose ratio,and serum level were compared according to the various genotypes of CYP3A5 and MDR1 polymorphisms in renal transplantation recipients,respectively.Results The dosage of tacrolimus in CYP3A5*3/*3(GG)kidney transplantation recipients within 4 weeks after kidney transplantation was lower than those of CYP3A5*1/*1(AA)and CYP3A5*1/*3(AG).The serum creatinine levels of patients whose tacrolimus concentration in the range of 10-13 ng/ml were close to the normal value.Conclusion CYP3A5 gene polymorphism affects the blood concentrations of tacrolimus in renal transplant recipients.No association has been found between the blood concentrations of tacrolimus and MDR1 gene polymorphism.Tacrolimus concentration in the range of 10-13 ng/ml might contribute to restore the early kidney graft function.

关 键 词：肾移植 他克莫司 肌酐 CYP3A5 MDR1 

分 类 号：R969.3[医药卫生—药理学]