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

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.

• Authors: Shao-qing Ni, Wei Zhao, Jue Wang, Su Zeng, Shu-qing Chen, Evelyne Jacqz-Aigrain, Zheng-yan Zhao
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 34 Issue 7 Pg. 969-75 (Jul 2013) ISSN: 1745-7254 [Electronic] United States
• PMID: 23624757 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Stanozolol
• Cyclosporine

Topics

• Adolescent
• Anemia, Aplastic (drug therapy, ethnology, physiopathology)
• Asian People (ethnology)
• Body Weight (drug effects, physiology)
• Child
• Child, Preschool
• Cyclosporine (administration & dosage, pharmacokinetics)
• Female
• Humans
• Immunosuppressive Agents (administration & dosage, pharmacokinetics)
• Infant
• Kidney Function Tests (methods)
• Male
• Metabolic Clearance Rate (drug effects, physiology)
• Prospective Studies
• Stanozolol (administration & dosage, pharmacokinetics)