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Acta Pharmacol Sin. 2013 Jul;34(7):969-75. doi: 10.1038/aps.2013.9. Epub 2013 Apr 29.

Population pharmacokinetics of ciclosporin in Chinese children with aplastic anemia: effects of weight, renal function and stanozolol administration.

Author information

1
Department of Clinical Pharmacology, the Children's Hospital of Zhejiang University School of Medicine and Zhejiang Key Laboratory for Diagnosis and Therapy of Neonatal Diseases, Hangzhou, China.

Abstract

AIM:

To develop a population pharmacokinetic model for the immunosuppressant ciclosporin in Chinese children with aplastic anemia and to identify covariates influencing ciclosporin pharmacokinetics.

METHODS:

A total of 102 children with either acquired or congenital aplastic anemia aged 8.8±3.6 years (range 0.9-17.6 years) were included. Therapeutic drug monitoring (TDM) data for ciclosporin were collected. The population pharmacokinetic model of ciclosporin was described using the nonlinear mixed-effects modeling (NONMEM) VI software. The final model was validated using bootstrap and normalized prediction distribution errors.

RESULTS:

A one-compartment model with first-order absorption and elimination was developed. The estimated CL/F was 15.1, which was lower than those of children receiving stem cell or kidney transplant reported in the West (16.9-29.3). The weight normalized CL/F was 0.45 (range: 0.27-0.70) Lh(-1)·kg(-1). The covariate analysis identified body weight, serum creatinine and concomitant administration of the anabolic steroid stanozolol as individual factors influencing the CL/F of ciclosporin.

CONCLUSION:

Our model could be used to optimize the ciclosporin dosing regimen in Chinese children with aplastic anemia.

PMID:
23624757
PMCID:
PMC4002619
DOI:
10.1038/aps.2013.9
[Indexed for MEDLINE]
Free PMC Article

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