【摘要】：目的應(yīng)用非線性混合效應(yīng)模型(NONMEM)考察中國新生兒患者萬古霉素群體藥動學(xué)特征。方法回顧性收集南京醫(yī)科大學(xué)附屬蘇州醫(yī)院新生兒患者91例,154個谷濃度數(shù)據(jù)建立群體藥動學(xué)模型。采用一級消除的一室模型進行數(shù)據(jù)擬合,并引入生理成熟度模型考察體重和年齡對清除率的影響。采用自舉法和正態(tài)預(yù)測分布誤差法(NPDE)進行最終模型評價。在模型應(yīng)用時,應(yīng)用最終模型及參數(shù)估算值,結(jié)合Monte Carlo法模擬,評價MIC為1 mg·L~(-1)時不同孕周、日齡和血清肌酐水平的典型患兒在不同給藥方案下的AUC_(0-24 h)/MIC≥400的比例。結(jié)果最終模型確定體重、矯正孕周和血清肌酐為影響清除率的主要因素。模型評價表明,模型參數(shù)估算可靠、模型穩(wěn)定。此外,血清肌酐低水平(15μmol·L~(-1))組有96%的患兒在指南推薦給藥方案下AUC_(0-24 h)/MIC未達標,可根據(jù)所建立的模型計算給藥劑量。結(jié)論本研究建立的新生兒萬古霉素群體藥動學(xué)模型可為國人新生兒人群的萬古霉素的個體化給藥提供參考。
[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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