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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Population Pharmacokinetic Modeling of Gentamicin in Pediatrics
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Population Pharmacokinetic Modeling of Gentamicin in Pediatrics

机译：儿科庆大霉素的人口药代动力学建模

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Abstract The primary objective of this work was to characterize the pharmacokinetics (PK) of gentamicin across the whole pediatric age spectrum from premature neonates to young adults with a single model by identifying significant clinical predictors. A nonlinear mixed‐effect population PK model was developed with retrospective therapeutic drug‐monitoring data. A total of 6459 drug concentration measurements from 3370 hospitalized patients were collected for model building (n?=?2357) and evaluation (n?=?1013). In agreement with previously reported models, a 2‐compartment model with first‐order elimination best described the drug PK. Patient‐specific factors significantly impacting gentamicin clearance included fat‐free mass, postmenstrual age, and serum creatinine (SCr). Based on our model, the deviation of the individual SCr from the age‐dependent expected mean SCr value (SCrM) can result in a 40% lower clearance in a patient with renal impairment than that in a patient with normal kidney function, with SCrM:SCr ratios between 0.16 and 3.2 in this study. Consistent with the known age‐dependent changes of the proportion of extracellular water in body weight, the inclusion of the impact of extracellular water maturation on the central volume of distribution was found to improve the model fitting significantly. In comparison with other published models, model evaluation suggested the developed model was the least biased and physiologically most representative. These results will be used to inform individualized initial dosing strategies and serve as a prior PK model for Bayesian updating and forecasting as individual clinical observations become available.
机译：摘要这项工作的主要目标是通过识别显着的临床预测因子，在整个小儿科的全部儿科患者中对整个小儿毒素的药代动力学（PK）的特征表征在整个小儿科的常见症中。具有回顾性治疗药物监测数据的非线性混合群体PK模型。从3370名住院患者中收集了6459次药物浓度测量，用于模型建筑物（n？= 2357）和评估（n？=？1013）。在与先前报告的模型同意，一系列具有一阶消除的2室模型最佳地描述了该药物PK。患者特异性因素显着影响庆大霉素清除包括无脂肪块，后期年龄和血清肌酐（SCR）。基于我们的模型，来自年龄依赖预期平均SCR值（SCRM）的个体SCR的偏差可能导致患者患者患者患者的间隙40％，而不是肾功能普通肾功能的患者：本研究中的SCR比率在0.16和3.2之间。符合已知的年龄依赖性变化的体重细胞外水比例的变化，发现细胞外水成熟对中央分布体积的影响，以显着改善模型拟合。与其他公开的模型相比，模型评估表明，开发的模型是最不偏见和生理学上的最具代表性的。这些结果将用于通知个体化的初始给药策略，并作为贝叶斯更新和预测的先前PK模型，因为个别临床观察可用。

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