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Population pharmacokinetics of cyclosporine in Chinese children receiving hematopoietic stem cell transplantation.
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2019-07-24 , DOI: 10.1038/s41401-019-0277-x Tai-Feng Li 1 , Lei Hu 2 , Xiao-Lu Ma 3 , Lin Huang 2 , Xue-Mei Liu 2 , Xing-Xian Luo 2 , Wan-Yu Feng 2 , Chun-Fu Wu 1
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2019-07-24 , DOI: 10.1038/s41401-019-0277-x Tai-Feng Li 1 , Lei Hu 2 , Xiao-Lu Ma 3 , Lin Huang 2 , Xue-Mei Liu 2 , Xing-Xian Luo 2 , Wan-Yu Feng 2 , Chun-Fu Wu 1
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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.
更新日期：2019-11-18
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