万古霉素在重症监护患者的群体药代动力学模型建立与验证

Establishment and validation of vancomycin population pharmacokinetic model for intensive care unit patients

目的建立适合重症监护患者的万古霉素群体药代动力学模型,用以指导其给药方案调整。方法收集54例重症监护患者的112个常规血药浓度监测数据,用NONMEM软件以非线性混合效应模型进行群体分析,建立单房室药代动力学模型。通过拟合优度评价及自举验证法进行模型的内部验证;收集35例重症监护患者的95个常规血药浓度监测数据,通过拟合优度参数法进行模型的外部验证。以评价最终模型的拟合性能。结果模型内部验证及外部验证的结果表明,模型结构稳定,能较好地预测万古霉素浓度的动态变化规律。结论万古霉素静脉注射给药后的体内过程符合单房室药代动力学的特征,美罗培南对万古霉素的清除率有显著影响。

Objective To establish the population pharmaeokinetic （PPK） model of vancomyein in intensive care unit （ICU） patients, for guiding the adjustment of dosage regimen. Methods A total of 112 routine blood vancomycin concentration monitoring data were collected from 54 cases of ICU patients. A nonlinear mixed effect modeling program was used to establish one - eompartment model with NONMEM software. Internal model validation by goodness -of- fit and bootstrap were performed to evaluate the robustness and prediction of the final model. Ninety -five routine blood vancomycin concentration monitoring data was collected from 35 cases of ICU patients, and the external validation of the model was performed by goodness - of - fit parameter method. Results The results of internal and external validation of the model showed that the model was stable and could predict the dynamic variation of vancomy- cin concentration well. Conclusion The in vivo process of vancomycin after intravenous administration in ICU patients was consistent with the single - compartment PPK model. The clearance of vancomycin was significandy influenced by meropenem.