新生儿万古霉素的群体药动学研究

发布时间：2019-03-30 19:05

【摘要】：目的应用非线性混合效应模型(NONMEM)考察中国新生儿患者万古霉素群体药动学特征。方法回顾性收集南京医科大学附属苏州医院新生儿患者91例,154个谷浓度数据建立群体药动学模型。采用一级消除的一室模型进行数据拟合,并引入生理成熟度模型考察体重和年龄对清除率的影响。采用自举法和正态预测分布误差法(NPDE)进行最终模型评价。在模型应用时,应用最终模型及参数估算值,结合Monte Carlo法模拟,评价MIC为1 mg·L~(-1)时不同孕周、日龄和血清肌酐水平的典型患儿在不同给药方案下的AUC_(0-24 h)/MIC≥400的比例。结果最终模型确定体重、矫正孕周和血清肌酐为影响清除率的主要因素。模型评价表明,模型参数估算可靠、模型稳定。此外,血清肌酐低水平(15μmol·L~(-1))组有96%的患儿在指南推荐给药方案下AUC_(0-24 h)/MIC未达标,可根据所建立的模型计算给药剂量。结论本研究建立的新生儿万古霉素群体药动学模型可为国人新生儿人群的万古霉素的个体化给药提供参考。
[Abstract]:Objective to investigate the pharmacokinetic characteristics of vancomycin population in Chinese newborn infants by using the nonlinear mixed effect model (NONMEM). Methods Ninety-one neonates in Suzhou Hospital affiliated to Nanjing Medical University were collected retrospectively and 154 valley concentration data were collected to establish a population pharmacokinetic model. The effects of body weight and age on clearance rate were investigated by using the first-order eliminated one-compartment model and the physiological maturity model. The final model was evaluated by using the bootstrap method and the normal predictive distribution error method (NPDE). When the model is applied, the final model and parameter estimation are used, and the Monte Carlo method is used to evaluate the different gestational weeks when the MIC is 1 mg 路L ~ (- 1). The ratio of AUC_ (0 / 24 h) / MIC 鈮，

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