中国临床药理学杂志2017，Vol.33Issue(17)：1660-1664,5.DOI:10.13699/j.cnki.1001-6821.2017.17.015
再生障碍性贫血患者体内环孢素的群体药代动力学研究
Population pharmacokinetics of cyclosporine in patients with aplastic anemia
摘要
Abstract
Objective To establish the population pharmacokinetics (PPK) of cyclosporine (CsA) in children and adults aplastic anemia patients,to compare the differences between the two models,and to provide reference for individualized medication in clinical practice.Methods CsA steady-state plasma concentration data from therapeutic drug monitoring we recollected retrospectively from 141 children patients and 93 adults patients,with a total of 932 plasma drug concentrations and clinical data.PPK model was set up by using the nonlinear mixed effects modeling (NONMEM) method.The influences of fixed effect such as demographic characteristics,blood routine examination,blood biochemical examination and drug combination on pharmacokinetic parameters were investigated.The final model was validated by the Bootstrap method.Results The final model formula of children patients was:CL/F =73.5 (TAMT/135)0.65 (AST/24)-0.3 (CREA/40)-0.24 (0.09) TBIL/10,V/F =6870(TAMT/135)0.89.The final model formulaof adults patients was:CL/F =48.9 (TAMT/193) 0.49,V/F =2790 (TAMT/193)-0.71.The resuits were validated to be effective and stable by Bootstrap method.Conclusion The PPK final model of CsA in aplastic anemia patients can be established using the NONMEM.关键词
环孢素/再生障碍性贫血/群体药代动力学/非线性混合效应模型法Key words
cyclosporine/aplastic anemia/population pharmacokinetics/nonlinear mixed effects modeling分类
医药卫生引用本文复制引用
刘世浩,陈亚南,徐善森,徐英宏,肇丽梅..再生障碍性贫血患者体内环孢素的群体药代动力学研究[J].中国临床药理学杂志,2017,33(17):1660-1664,5.基金项目
国家自然科学基金资助项目(81673510) （81673510）
