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. © 2013 CPS and SIMM. All rights reserved.
CITATION STYLE
Ni, S. Q., Zhao, W., Wang, J., Zeng, S., Chen, S. Q., Jacqz-Aigrain, E., & Zhao, Z. Y. (2013). Population pharmacokinetics of ciclosporin in Chinese children with aplastic anemia: Effects of weight, renal function and stanozolol administration. Acta Pharmacologica Sinica, 34(7), 969–975. https://doi.org/10.1038/aps.2013.9
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