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

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AUC0～12h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AUC0～12h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.

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

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.