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.
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 steroidstanozolol 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: S Irtan; F Saint-Marcoux; A Rousseau; D Zhang; V Leroy; P Marquet; E Jacqz-Aigrain Journal: Ther Drug Monit Date: 2007-02 Impact factor: 3.681
Authors: W Zhao; V Elie; G Roussey; K Brochard; P Niaudet; V Leroy; C Loirat; P Cochat; S Cloarec; J L André; F Garaix; A Bensman; M Fakhoury; E Jacqz-Aigrain Journal: Clin Pharmacol Ther Date: 2009-10-28 Impact factor: 6.875
Authors: A J Willemze; S C Cremers; R C Schoemaker; A C Lankester; J den Hartigh; J Burggraaf; J M Vossen Journal: Br J Clin Pharmacol Date: 2008-04-30 Impact factor: 4.335