title: Population pharmacokinetics of ciclosporin in Chinese children with aplastic anemia: effects of weight, renal function and stanozolol administration.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our model could be used to optimize the ciclosporin dosing regimen in Chinese children with aplastic anemia.
authors.affiliation: 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.
authors.forename: Shao-qing
authors.initials: SQ
authors.lastname: Ni
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
authors.forename: Shu-qing
authors.initials: SQ
authors.lastname: Chen
authors.forename: Evelyne
authors.initials: E
authors.lastname: Jacqz-Aigrain
authors.forename: Zheng-yan
authors.initials: ZY
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000188:drug therapy / Q000208:ethnology / Q000503:physiopathology*; D044466:Asian People / Q000208:ethnology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007223:Infant; D007677:Kidney Function Tests / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D011446:Prospective Studies; D013197:Stanozolol / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D013197:Stanozolol; D016572:Cyclosporine