外周血单个核细胞及移植活检组织中他克莫司浓度与全血浓度和不良反应及临床疗效相关性研究进展  

Research Progress on the Correlation of Tacrolimus Concentration in Peripheral Blood Mononuclear Cells and Transplanted Biopsy Tissue with Whole Blood Concentration,Adverse Reactions,and Clinical Efficacy

作　　者：郭朋朋 张蕊 刘亚妮[1] 师少军[1,2] GUO Pengpeng;ZHANG Rui;LIU Yani;SHI Shaojun(Department of Pharmacy,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;Department of Pharmacy,the First People's Hospital of Jiangxia District,Wuhan city(Union Jiangnan Hospital),Wuhan 433000,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,武汉430022 [2]武汉市江夏区第一人民医院(协和江南医院)药学部,武汉433000

出　　处：《医药导报》2023年第6期898-903,共6页Herald of Medicine

基　　金：国家自然科学基金资助项目(82173902,81874326);湖北省卫健委中医药科研项目(ZY2019Z004);北京医学奖励基金会项目(YXJL-2018-0095-0068);国家重点研发计划资助(2017YFC0909900)。

摘　　要：第2代钙调磷酸酶抑制剂他克莫司(TAC)作为器官移植患者术后一线免疫抑制剂,治疗窗窄、个体差异大。因此,临床采用血药浓度监测对TAC进行个体化剂量调整。即使TAC全血浓度处于治疗窗内,仍有移植患者发生排斥反应或其他不良反应。说明全血TAC浓度并不能准确反映TAC体内的药理效应。因此有研究者提出采用检测靶细胞-外周血单个核细胞内或移植活检组织内TAC浓度来替代血药浓度,更准确反映器官移植患者体内免疫抑制情况。该文主要对外周血单个核细胞内及移植活检组织内TAC浓度与全血TAC浓度相关性进行分析,同时对细胞内或组织内TAC浓度能否预测移植患者术后排斥反应的发生、与钙调磷酸酶活性相关性以及TAC相关肾毒性展开讨论。Tacrolimus,a second-generation calcineurin inhibitor(TAC),is a first-line immunosuppressant after organ transplantation with a narrow therapeutic window and significant individual differences.Therefore,individualized dose adjustment of tacrolimus is carried out by monitoring the blood concentration in clinical use.However,even if the whole blood concentration of TAC is within the therapeutic window,transplant patients will still experience rejection or other adverse reactions.It indicates that the concentration of TAC in whole blood cannot accurately reflect its pharmacological effects in vivo.Therefore,some researchers proposed to use the detection of TAC concentration in target cells-peripheral blood mononuclear cells or transplanted biopsy tissue to replace the blood drug concentration,to accurately reflect the immunosuppression in organ transplantation patients.This review mainly summarizes and analyzes the correlation between TAC concentration in peripheral blood mononuclear cells and in transplant biopsy tissue and whole blood TAC concentration.It also discusses whether intracellular or intratissue TAC concentration can predict the occurrence of postoperative rejection in transplant patients,calcineurin activity and TAC-related nephrotoxicity.

关 键 词：他克莫司 治疗药物监测 外周血单个核细胞活检 活检组织 排斥反应 肾毒性 

分 类 号：R979.5[医药卫生—药品] R617[医药卫生—药学]