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

作　　者：Shao-qing NI Wei ZHAO Jue WANG Su ZENG Shu-qing CHEN Evelyne JACQZ-AIGRAIN Zheng-yan ZHAO 

机构地区：[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 310003, China [2]Department of Pediatric Pharmacology and Pharmaco- genetics, Hopital Robert Debro, Universito Paris Diderot, Assistance Publique - H6pitaux de Paris, Paris, France [3]Clinical Investigation Center CIC9202, INSERM, Paris, France [4]Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China [5]Department of Pediatrics, the Children's Hospital of Zhejiang University School of Medicine and Zhejiang Key Laboratory for Diagnosis and Therapy of Neonatal Diseases, Hangzhou 310003, China

出　　处：《Acta Pharmacologica Sinica》2013年第7期969-975,共7页中国药理学报（英文版）

摘　　要：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） Vl 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 CI_/F was 0.45 （range： 0.27-0.70） L-h-l-kg-1. The covariate analysis identified body weight, serum creatinine and concomitant adminis- tration 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） Vl 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 CI_/F was 0.45 （range： 0.27-0.70） L-h-l-kg-1. The covariate analysis identified body weight, serum creatinine and concomitant adminis- tration 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.

关 键 词：CICLOSPORIN IMMUNOSUPPRESSANT aplastic anemia population pharmacokinetics STANOZOLOL serum creatinine PEDIATRICS 

分 类 号：S859.796[农业科学—临床兽医学] TS974.22[农业科学—兽医学]