【摘要】 目的建立再生障碍性贫血（再障）儿童和成人患者服用环孢素的群体药代动力学（PPK）模型,比较两个模型之间的差异。方法回顾性收集口服环孢素的141例儿童和93例成人再障患者的血药浓度数据及临床资料共932份。用非线性混合效应模型（NONMEM）法分别建立儿童和成人患者PPK模型,并考察人口学信息、血常规、血生化和联合用药等固定效应对药代动力学参数的影响。最终模型采用Bootstrap法进行内部验证。结果儿童患者最终模型公式为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。成人患者最终模型公式为CL/F=48.9（TAMT/193）^0.49,V/F=2790（TAMT/193）^-0.71。Bootstrap法对模型内部验证结果显示模型稳定可靠。结论用NONMEM法建立了再障患者应用环孢素的PPK模型。更多还原

【Abstract】 Objective To establish the population pharmacokinetics（ PPK） of cyclosporine（ Cs A） 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 Cs A 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 results were validated to be effective and stable by Bootstrap method.Conclusion The PPK final model of Cs A in aplastic anemia patients can be established using the NONMEM.更多还原