肾移植患者全血和外周血单个核细胞内他克莫司的药动学  

Pharamcokinetics of tacrolimus in peripheral blood mononuclear cell in Chinese renal transplant allograft recipients

作　　者：刘晓雪[1] 王雨萍 石浩强[1] 周佩军[2] 陈冰[1] LIU Xiaoxue;WANG Yuping;SHI Haoqiang;ZHOU Peijun;CHEN Bing(Department of Pharmacy,Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200025,China;Center of Organ Transplantation,Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院药剂科,上海200025 [2]上海交通大学医学院附属瑞金医院移植中心,上海200025

出　　处：《中国临床药学杂志》2023年第8期561-565,共5页Chinese Journal of Clinical Pharmacy

基　　金：国家自然科学基金(编号81973387)。

摘　　要：目的分析中国肾移植患者他克莫司(TAC)在全血(WB)和外周血单个核细胞(PBMC)中的药动学,并探索二者之间的关系。方法采集27例接受TAC在内的三联免疫疗法肾移植患者在给予TAC后0、0.5、1、1.5、2、4、6、8、10、12 h的WB标本,提取PBMC,采用LC-MS/MS法测定WB与PBMC中TAC浓度,WinNonlin软件以非房室法计算WB和PBMC中的TAC药动学参数。结果肾移植患者WB与PBMC内的AUC_(0-12 h)分别为125.05(40.32-306.6)ng·h·mL^(-1)和6.25(0.31-30.64)ng·h·nmol^(-1),C_(max)分别为21.30(0.25-34.50)ng·mL^(-1)和1.28(0.07-6.49)ng·nmol^(-1)。WB与PBMC中AUC_(0-12 h)(r^(2)=0.4226)、C_(0)(r^(2)=0.5854)和C_(max)(r^(2)=0.4226)存在一定相关性(P<0.05)。结论中国肾移植患者WB中与PBMC中TAC的暴露量具有一定相关性,在特定患者中监测PBMC的TAC暴露量可以作为TDM的一种方式。AIM To investigate of the pharmacokinetics of tacrolimus(TAC)in whole blood(WB)and peripheral blood mononuclear cells(PBMC)in Chinese renal transplant patients,and to explore their relationship.METHODS There were 27 renal transplant patients receiving triple immunosuppressive therapy including TAC were enrolled.Blood samples were collected at 0,0.5,1,1.5,2,4,6,8,10,12 h after receiving TAC.PBMC was extracted from the whole blood samples.LC-MS/MS method was employed to measure TAC concentrations in both WB and PBMC.Pharmacokinetic parameters of TAC in WB and PBMC were calculated using non-compartmental analysis with WinNonlin software.RESULTS The AUC_(0-12 h) levels in WB and PBMC of renal transplant patients were 125.05(40.32-306.6)ng·h·mL^(-1) and 6.25(0.31-30.64)ng·h·nmol^(-1),respectively.The C_(max) values were 21.30(0.25-34.50)ng·mL^(-1) and 1.28(0.07-6.49)ng·nmol^(-1).There was a certain correlation between WB and AUC_(0-12 h)(r^(2)=0.4226),C_(0)(r^(2)=0.5854)and C_(max)(r^(2)=0.4226)in PBMC(P<0.05).CONCLUSION There is a certain correlation between WB and TAC exposure in PBMC in Chinese renal transplant patients.Monitoring TAC in PBMC can serve as an alternative biomarker for TDM in specific patients.

关 键 词：他克莫司 外周血单个核细胞 药动学参数 肾移植 

分 类 号：R699.2[医药卫生—泌尿科学]