Cyclosporine (CsA) is characterized by a narrow therapeutic window and high interindividual pharmacokinetic variability,particularly in juvenile patients.The aims of this study were to build a population pharmacokinetic model of CsA in Chinese children with hematopathy who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify covariates affecting CsA pharmacokinetics.A total of 86 Chinese children aged 8.4 ± 3.8 years (range 1.1-16.8 years) who received allo-HSCT were enrolled.Whole blood samples were collected before allo-HSCT.Genotyping was performed using an Agena MassARRAY system.A total of 1010 trough plasma concentration values of CsA and clinical data were collected.The population pharmacokinetic model of CsA was constructed using nonlinear mixed-effects modeling (NONMEM) software.The stability and performance of the final model were validated using bootstrapping and normalized prediction distribution errors.We showed that a one-compartment model with first-order elimination adequately described the pharmacokinetics of CsA.The typical values for clearance (CL) and volume of distribution (V) were 42.3 L/h and 3100 L,respectively.Body weight,postoperative days,CYP3A4*1 G genotype,estimated glomerular filtration rate and coadministration of triazole antifungal drugs were identified as significant covariates for CL.Weight and postoperative days were significant covariates for the V of CsA.Our model can be adopted to optimize the CsA dosing regimen for Chinese children with hematopathy receiving allo-HSCT.
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