老年患者万古霉素群体药代动力学模型验证

Evaluation of the population pharmacokinetic models of vancomycin in geriatric patients

目的:利用已发表的成人万古霉素群体药代动力学模型对本院使用万古霉素的老年患者治疗药物监测数据进行拟合;探讨已发表的模型对不同临床机构的适用性,选择较为适合本院老年患者的万古霉素群体药代动学模型。方法:分析已发表的成人万古霉素群体药代动力学模型,提取人口学信息及模型参数,将模型参数固定后,利用NONMEM 7.3.0.(Icon Development Solution,USA)软件及PDx-Pop Version 5软件进行拟合,并用RStudio软件作图。根据实测浓度-预测浓度(DV-PRED)图及可视化预测检验(VPC)评估拟合效果。结果:共收集2014-2015年42例老年患者88个稳态谷浓度点,年龄范围为66~93岁;共检索到15个成人万古霉素群体药代动力学模型,一房室模型6个,二房室模型9个。对一房室模型进行拟合,模型拟合图形显示模型2、5及6的拟合效果较好,其中模型5为老年人模型。结论:可以尝试利用拟合结果良好的模型在本院进行前瞻性临床实践,并逐步建立本院老年患者的万古霉素群体模型。

Objective： To simulate the therapeutic drug monitoring data of vancomycinin geriatric patients in Peking University First Hospital with published adult population pharmacokinetic models of vancomycinthus to investigate the transfer ability of published models to different clinical settings and provide support for selecting the appropriate population pharma cokinetic model specificfor the geriatric patientsin our hospital. Methods： The published adult population pharmacokinetic models of vancomycin were analyzed, and the patient demographics and model information were extracted. After fixing model parameters, the data were simulated with NONMEM 7.3.0.（lcon Development Solution, USA） and PDx-Pop Version 5.Graphs were drawn with R Studio. The simulation performance was evaluated by the observed concentration-predicted concentration graph （DV-PRED graph）and VisualPredictive Checks （VPC）. Results：A total of 88 trough concentrations of vancomyein from 42 geriatric patients were collected between 2014and 2015. The ages of the patients varied from 66 to 93 years. Fifteen adult population pharmacokinetic models of vancomycin were searched, among which six were one-compartment models and nine were two-compartment ones. One-compartment models were simulated. According to the stimulation performance, models 2, 5 and 6 had better performance. Besides, model 5 was the model for geriatric people. Conclusion： The published model with better performance may be used to carry out prospective clinical practice in our hospital and the population pharmacokinetic model of vancomycinspecific for the geriatric patients in our hospitalcan be gradually established.