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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)~(0.6)5(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。
Objective To establish a population pharmacokinetic (PPK) model of cyclosporine in children and adults with aplastic anemia (aplastic anemia) and to compare the differences between the two models. Methods A total of 932 plasma concentrations and clinical data of 141 children with cyclosporine and 93 adults with aplastic anemia were retrospectively collected. The PPK model of children and adults were established by nonlinear mixed effect model (NONMEM), and the effects of fixed effects such as demographic information, blood routine, blood biochemistry and combination therapy on the pharmacokinetic parameters were investigated. The final model is Bootstrap method for internal verification. Results The formula of the final model of children was CL / F = 73.5 (TAMT / 135) ~ (0.6) 5 (AST / 24) -0.3 (CREA / 40) -0.24 (0.09) ), V / F = 6870 (TAMT / 135) ~ (0.89). The final model of adult patients was CL / F = 48.9 (TAMT / 193) ~ (0.49), V / F = 2790 (TAMT / 193) ~ (-0.71). Bootstrap test results show that the model is stable and reliable. Conclusion The PPK model of cyclophosphamide in patients with aplastic anemia was established by NONMEM.