Int J Clin Pharmacol Ther. 2024 Nov;62(11):507-516. doi: 10.5414/CP204561.
Tacrolimus (TAC) is a first-line immunosuppressant to prevent allograft rejection. tablet is widely used as a TAC-sparing agent in China that could significantly elevate TAC exposure. However, insufficient data support the dose recommendation of TAC when co-administered with .
A total of 305 adult renal transplant patients with 2,541 TAC trough concentrations (C) were enrolled for population pharmacokinetic (PPK) modeling. polymorphism was genotyped, and corresponding clinical factors were recorded. Nonlinear mixed-effects modeling and Monte Carlo simulation were used for dose recommendation. PK parameters were calculated based on one-compartment model with first-order absorption and elimination.
The estimated total clearance (CL/F) and volume of distribution (V/F) of TAC were 23.84 L/h and 1,075.96 L, respectively. , genotype, hematocrit (HCT), and weight were found to have a significant influence on CL/F. CL/F was significantly lower in the individuals who were non-expressers and received TAC together with . genotype (expressers or non-expressers), body weight (40 - 80 kg), and hematocrit (20 - 40%) were selected as the specific clinical scenarios, and the starting dose of TAC ranged from 1.5 to 4.5 mg when co-administered with .
We establish a TAC PPK model comprising as a covariate in renal transplant recipients and recommend an initial dose of TAC when co-administered with , which could provide reference for the individualized regimens of TAC.
他克莫司（TAC）是预防移植物排斥反应的一线免疫抑制剂。片剂在中国被广泛用作 TAC 节约剂，可以显著提高 TAC 的暴露量。然而，当与 合用时，TAC 的剂量推荐缺乏足够的数据支持。
共纳入 305 例成人肾移植患者，共 2541 次他克莫司谷浓度（C）进行群体药代动力学（PPK）建模。对 多态性进行基因分型，并记录相应的临床因素。采用非线性混合效应模型和蒙特卡罗模拟进行剂量推荐。PK 参数基于一室模型，具有一级吸收和消除。
TAC 的总清除率（CL/F）和分布容积（V/F）分别估计为 23.84 L/h 和 1075.96 L。发现 基因型、红细胞压积（HCT）和体重对 CL/F 有显著影响。在非表达者和同时接受 TAC 和 基因型（表达者或非表达者）的个体中，CL/F 显著降低。体重（40-80kg）和红细胞压积（20-40%）被选为特定的临床情况，当与 合用时，TAC 的起始剂量范围为 1.5-4.5mg。
我们建立了一个包含 作为肾移植受者的协变量的 TAC PPK 模型，并推荐了与 合用时 TAC 的起始剂量，这可为 TAC 的个体化治疗方案提供参考。
