Population pharmacokinetics of cyclosporine in Chinese children receiving hematopoietic stem cell transplantation.
Acta Pharmacol Sin
; 40(12): 1603-1610, 2019 Dec.
Article
en En
| MEDLINE
| ID: mdl-31341257
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Trasplante Homólogo
/
Ciclosporina
/
Trasplante de Células Madre Hematopoyéticas
/
Enfermedad Injerto contra Huésped
/
Inmunosupresores
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Año:
2019
Tipo del documento:
Article