万古霉素群体药动学模型在神经外科重症患者中的应用

发布时间：2018-11-21 20:03

【摘要】：目的验证通过非线性混合效应模型法(NONMEM)软件建立的万古霉素群体药动学模型在神经外科重症患者中应用的有效性和实用性。方法回顾性收集2013年3月—2014年3月南京鼓楼医院神经外科重症加护病房中给予万古霉素治疗患者的性别、年龄、体重、血肌酐和血白蛋白数值,通过前期建立的群体药动学模型,计算特定给药剂量下万古霉素的稳态血药谷浓度预测值,并与实际测量值比较,进而统计学分析验证。结果共收集患者42例,测得万古霉素血药谷浓度53份,平均谷浓度为10.9 mg/L,范围为1.6~49.1 mg/L。群体药动学模型的预测值与实际测量值有显著相关性(r=0.857,P0.001),平均绝对百分比误差(MAPE)为0.407 9,预测值的95%置信区间为9.36~14.07,实测值的95%置信区间为8.92~14.32。结论该群体药动学模型可以用于神经外科重症患者给予万古霉素前的预测和药物剂量的指导。但由于神经外科危重症患者昏迷,体重估计误差较大(约30%),同时对比剂和利尿药导致的肾功能改变影响结果。通过调整使用方法,预测准确率提高到近70%。
[Abstract]:Objective to verify the effectiveness and practicability of vancomycin population pharmacokinetic model established by nonlinear mixed effect model method (NONMEM) in patients with severe neurosurgery. Methods Sex, age, body weight, serum creatinine and serum albumin were collected retrospectively from March 2013 to March 2014 in the intensive care unit of neurosurgery department of Nanjing Gulou Hospital. Based on the population pharmacokinetic model established in the early stage, the predicted values of vancomycin's steady-state blood drug concentration under specific dosage were calculated, and compared with the actual measured values, and then verified by statistical analysis. Results A total of 42 patients were collected and 53 samples of vancomycin were determined. The average concentration of vancomycin was in the range of 10.9 mg/L, 1.6 mg/L. and 49.1 mg/L., respectively. The predicted value of the population pharmacokinetic model was significantly correlated with the actual measured value (r = 0.857p 0.001). The average absolute percentage error (MAPE) was 0.407, and the 95% confidence interval of the predicted value was 9.36 卤14.07. The 95% confidence interval of the measured value is 8.92 卤14.32. Conclusion the pharmacokinetic model can be used to predict vancomycin and drug dosage in patients with severe neurosurgery. However, due to coma, weight estimation error was larger (about 30%) in critically ill patients in neurosurgery, and the effects of contrast agent and diuretic on renal function were also observed. By adjusting the use of the method, the accuracy of prediction is improved to nearly 70.
【作者单位】：南京大学医学院附属鼓楼医院神经外科;南京大学医学院附属鼓楼医院药学部;
【基金】：南京市医学科技发展资金 2012年南京市卫生局“南京市卫生青年人才培养工程”第二层次
【分类号】：R969

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