老年患者替考拉宁群体药动学模型的建立及临床应用

目的 本研究应用非线性混合效应法(NONMEM)建立中国老年患者替考拉宁PPK模型.方法 收集102名老年患者共150个替考拉宁的血药浓度,采用一室模型建立替考拉宁的基础模型,分别考察SEX、AGE、WT、SCr、BUN、CCr等协变量对固定效应参数V、CL的影响,建立群体药动学最终模型.对最终模型拟合优度及稳定性进行...

Population Pharmacokinetic and Individualized Administration of Teicoplanin in Eldly Patients

OBJECTIVE To establish a PPK model of teicoplanin in Chinese elderly patients by non-linear mixed effect method. METHODS The plasma concentration of teicoplanin was collected from 102 elderly patients and 150 plasma samples. The model of teicoplanin was established by one compartment model. The influence of SEX, AGE, WT, SCR, BUN, CCR and other covariates on the fixed effect parameters V and CL was investigated respectively to establish final model.The goodness of fit and stability of the final model were evaluated: the goodness of fit of the model was judged by R language graphing, and the stability and predictive ability of the model were judged by Bootstrap and NPDE methods. RESULTS The final model of teicoplanin for elderly patients was CL=1.30×(CLcr/80.4)^(0.572 L·h^-1),V=86.9 L;the apparent clearance of teicoplanin was 1.30 L·h^-1and the apparent distribution volume was 86.9 L. The goodness of fit of the final model was good by R language graphing. The absolute value of relative deviation of Bootstrap method was between 0.3% and 7.2%, and the robustness rate of the model was 94.4%, indicating good stability of the model, and the good prediction of the model was shown by the NPDE method. CONCLUSION The population pharmacokinetic model of teicoplanin for the elderly established in this study is authentic and reliable. CLcr has a significant effect on the clearance of teicoplanin.