Population pharmacokinetics of ciclosporin in Chinese children with aplastic anemia: effects of weight, renal function and stanozolol administration
Population pharmacokinetics of ciclosporin in Chinese children with aplastic anemia: effects of weight, renal function and stanozolol administration
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中国再生障碍性贫血儿童中环孢素的群体药代动力学：体重、肾功能和康力龙给药的影响
DOI：
10.1038/aps.2013.9
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发表时间：
2013-07-01
影响因子：
8.2
通讯作者：
Zhao, Zheng-yan
中科院分区：
文献类型：
--
作者：
Ni, Shao-qing;Zhao, Wei;Zhao, Zheng-yan
目的：建立免疫抑制剂环孢素在中国儿童再生障碍性贫血（再障）中的群体药代动力学模型，并分析影响环孢素药代动力学的协变量。收集环孢素的治疗药物监测（TDM）数据。采用非线性混合效应模型（NONMEM）VI软件建立环孢素的群体药代动力学模型。结果：建立了一个具有一级吸收和消除的一室模型。估计的CL/F为15.1，低于西方报道的接受干细胞或肾移植的儿童（16.9-29.3）。体重标准化CL/F为0.45（范围：0.27-0.70）Lh− 1· kg− 1。协变量分析确定体重，血清肌酐和合并使用的合成代谢类固醇司坦唑醇作为影响CL/F的环孢素。结论：我们的模型可以用来优化环孢素的给药方案在中国儿童再生障碍性贫血。
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.