Chen Xiao, Wang Dongdong, Zheng Feng, Zhai Xiaowen, Xu Hong, Li Zhiping
Department of Pharmacy, Children's Hospital of Fudan University, Shanghai, China.
Department of Hematology and Oncology, Children's Hospital of Fudan University, Shanghai, China.
Front Pharmacol. 2022 Jul 22;13:869939. doi: 10.3389/fphar.2022.869939. eCollection 2022.
The present study aimed to explore the population pharmacokinetics and initial dose optimization of tacrolimus in children with severe combined immunodeficiency (SCID) undergoing hematopoietic stem cell transplantation (HSCT). Children with SCID undergoing HSCT treated with tacrolimus were enrolled for analysis. Population pharmacokinetics of tacrolimus was built up by a nonlinear mixed-effects model (NONMEM), and initial dose optimization of tacrolimus was simulated with the Monte Carlo method in children weighing <20 kg at different doses. A total of 18 children with SCID undergoing HSCT were included for analysis, with 130 tacrolimus concentrations. Body weight was included as a covariable in the final model. Tacrolimus CL/F was 0.36-0.26 L/h/kg from body weights of 5-20 kg. Meanwhile, we simulated the tacrolimus concentrations using different body weights (5-20 kg) and different dose regimens (0.1-0.8 mg/kg/day). Finally, the initial dose regimen of 0.6 mg/kg/day tacrolimus was recommended for children with SCID undergoing HSCT whose body weights were 5-20 kg. It was the first time to establish tacrolimus population pharmacokinetics in children with SCID undergoing HSCT; in addition, the initial dose optimization of tacrolimus was recommended.
本研究旨在探讨接受造血干细胞移植（HSCT）的重症联合免疫缺陷（SCID）患儿他克莫司的群体药代动力学及初始剂量优化。纳入接受他克莫司治疗的HSCT的SCID患儿进行分析。采用非线性混合效应模型（NONMEM）建立他克莫司的群体药代动力学，并采用蒙特卡洛方法模拟不同剂量下体重<20 kg患儿他克莫司的初始剂量优化。共纳入18例接受HSCT的SCID患儿进行分析，获得130个他克莫司血药浓度数据。最终模型纳入体重作为协变量。体重5 - 20 kg患儿他克莫司的清除率/分布容积（CL/F）为0.36 - 0.26 L/h/kg。同时，我们模拟了不同体重（5 - 20 kg）和不同给药方案（0.1 - 0.8 mg/kg/天）下的他克莫司血药浓度。最后，推荐体重5 - 20 kg接受HSCT的SCID患儿他克莫司初始给药方案为0.6 mg/kg/天。这是首次建立接受HSCT的SCID患儿他克莫司的群体药代动力学；此外，还给出了他克莫司初始剂量优化建议。
