Population pharmacokinetics of tacrolimus in children with nephrotic syndrome

作者：Hao, Guo-Xiang; Huang, Xin; Zhang, Dong-Feng; Zheng, Yi; Shi, Hai-Yan; Li, Yan; Jacqz-Aigrain, Evelyne; Zhao, Wei^*

来源：British Journal of Clinical Pharmacology, 2018, 84(8): 1748-1756.

DOI：10.1111/bcp.13605

• children
• nephrotic syndrome
• pharmacokinetics
• tacrolimus

AimsNephrotic syndrome (NS) is the most common clinical manifestation of glomerular disease in children. Currently, tacrolimus (TAC) is widely used in children with NS. However, pharmacokinetic data in children with nephrotic syndrome is limited. This study was intended to evaluate the population pharmacokinetics (PPK) of TAC in paediatric NS and to optimize dosing regimen. @@@ MethodsBlood samples from NS children treated with TAC were collected and the blood concentrations of TAC were detected using HPLC-MS/MS. A PPK model was developed using NONMEM software. Pharmacogenetic analysis was carried out in the CYP3A5 gene. @@@ ResultsThe data from 28 children were used for PPK analysis. A one-compartment model and first-order elimination were accorded with the TAC data in paediatric NS. A covariate analysis showed that body weight and CYP3A5 genotype significantly affected TAC pharmacokinetics. Monte Carlo simulation indicated that NS children with CYP3A5*33 receiving 0.10mgkg(-1)dose(-1) twice daily and NS children with CYP3A5*1 receiving 0.25mgkg(-1)dose(-1) twice daily TAC could achieve the target concentrations of 5-10ngml(-1). @@@ ConclusionThe PPK of TAC was estimated in children with NS and a CYP3A5 genotype-based dosing regimen was set up based on simulations.

• 出版日期2018-8
• 单位山东大学; 河北省儿童医院; 山东省千佛山医院