有限取样法估算中国肾移植患者单个核细胞内他克莫司的暴露量  

Limited Sampling Strategy for Estimation of Tacrolimus PBMC Exposure in Renal Transplant Patients

作　　者：王曦晗 邵琨[2] 安会敏[2] 周佩军[2] 陈冰[1] WANG Xihan;SHAO Kun;AN Huimin;ZHOU Peijun;CHEN Bing(Department of Pharmacy,Rui-Jin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Center for Organ Transplantation,Rui-Jin Hospital,Shanghai Jiao Tong 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：《药学与临床研究》2021年第5期355-359,共5页Pharmaceutical and Clinical Research

基　　金：国家自然科学基金(81973387)。

摘　　要：目的:建立预测肾移植患者服用他克莫司后外周血单个核细胞(PBMC)内暴露量的有限取样法(LSS)模型。方法:23例接受包括他克莫司在内的三联免疫疗法的肾移植患者,收集给药后0、0.5、1、1.5、2、4、6、8、10、12 h全血标本提取PBMC,采用LC-MS/MS法测定PBMC中他克莫司浓度。以多元线性分析法,获得他克莫司AUC0~12 h的LSS估算模型。用Bland-Altman评价模型的预测值和实际测量值的一致性。结果:建立了包含1~4个采样时间点的LSS模型(r2=0.570~0.989)。预测他克莫司AUC0~12 h的最佳模型为C2-C4-C6-C10(r2=0.989)。C0.5-C6模型(r2=0.849)则适用于短期需要监测的门诊患者。结论:由2-4个时间点组成的LSS模型是评估中国肾移植患者他克莫司AUC0~12 h的有效方法,可为临床监测他克莫司细胞内暴露量提供参考。Objectives:To develop a limited sampling strategy(LSS)for accurate prediction of the intracellular tacrolimus(TAC)exposure in renal transplant patients.Methods:Whole blood samples of 23 renal transplant patients who received triple immunotherapy were collected 0,0.5,1,1.5,2,4,6,8,10 and 12 h after TAC administration.Peripheral blood mononuclear cells(PBMC)were extracted from the whole blood samples.TAC concentrations in PBMC were measured by an LC-MS/MS method.Multiple linear regression analysis was used to determine LSS models for estimation of TAC AUC0-12 h.The selected models were validated by the Bland-Altman method.Results:LSS models with 1,2,3 or 4 blood time points were established(r2=0.570-0.989).The best model for predicting TAC AUC0-12 h was C2-C4-C6-C10(r2=0.989).The model with C0.5-C6(r2=0.849)could be used for outpatients who need monitoring in a short period.Conclusions:The LSS models consisting of 2-4 time points are effective approaches for estimating TAC AUC0-12 h in Chinese renal transplant patients.This approach may provide convenient clinical monitoring of TAC intracellular exposure.

关 键 词：他克莫司 外周血单个核细胞 药-时曲线下面积(AUC) 有限取样法 

分 类 号：R969.1[医药卫生—药理学]