Department of Pharmacy, Children's Hospital of Fudan University, Shanghai, China.
Department of Pharmacy, The People's Hospital of Jiangyin, Jiangyin, China.
J Clin Pharm Ther. 2019 Aug;44(4):611-617. doi: 10.1111/jcpt.12828. Epub 2019 Mar 12.
Tacrolimus is widely used for kidney transplantation in children. However, the narrow therapeutic window and considerable interindividual and intraindividual variabilities make tacrolimus untoward to design an optimum dosage for paediatric personalized medicine. Our research aims to establish the tacrolimus population pharmacokinetics (PPK) of Chinese paediatric kidney transplantation patients and to distinguish covariates impacting variabilities.
Chinese paediatric kidney transplantation patients treated with tacrolimus between January 2014 and April 2018 from Children's Hospital of Fudan University were retrospectively analysed. A total of 51 Chinese paediatric kidney transplantation patients were analysed using non-linear mixed effects modelling (NONMEM). The effects of population characteristics, biological features and drug combination were assessed. The final PPK model was evaluated using visual inspection of routine diagnostic plots and the internal validation method of bootstrap.
Our data met the condition of a one-compartment model, and the final model was CL/F = 32.7 × (WT/70) × (1 - WZ × 0.341) × (HGB/97) ; V/F = 1890 × (WT/70) × (POD/57) , where WT, WZ, HGB and POD were weight, Wuzhi capsule (extracted from schisandra sphenanthera, whose primary efficient constituents are schisantherin A, schisandrol B, schisandrin etc, and often used to treat drug-induced hepatitis in Chinese organ transplant patients), haemoglobin and post-transplant day, respectively.
The tacrolimus PPK model in Chinese paediatric kidney transplantation patients was developed, and Wuzhi capsule and haemoglobin influence tacrolimus elimination in paediatric kidney transplantation patients.
他克莫司在儿童肾移植中被广泛应用。然而，其治疗窗较窄，个体间和个体内差异较大，这使得他克莫司在设计儿科个体化药物的最佳剂量方面具有挑战性。我们的研究旨在建立中国儿童肾移植患者他克莫司的群体药代动力学（PPK），并区分影响变异性的协变量。
回顾性分析 2014 年 1 月至 2018 年 4 月在复旦大学附属儿科医院接受他克莫司治疗的中国儿童肾移植患者。采用非线性混合效应模型（NONMEM）对 51 例中国儿童肾移植患者进行分析。评估了人群特征、生物学特征和药物组合的影响。通过常规诊断图的视觉检查和自举法的内部验证方法来评估最终 PPK 模型。
我们的数据符合单室模型的条件，最终模型为 CL/F=32.7×（WT/70）×（1-WZ×0.341）×（HGB/97）；V/F=1890×（WT/70）×（POD/57），其中 WT、WZ、HGB 和 POD 分别为体重、五指胶囊（五味子的提取物，其主要有效成分包括五味子甲素、五味子醇 B、五味子酯等，常用于治疗中国器官移植患者的药物性肝炎）、血红蛋白和移植后天数。
建立了中国儿童肾移植患者他克莫司的 PPK 模型，五指胶囊和血红蛋白影响儿童肾移植患者他克莫司的消除。
