Lugo G, Castañeda-Hernández G
Departamento de Farmacología y Toxicología, Instituto Politécnico Nacional, Mexico City, Mexico.
Ther Drug Monit. 1997 Jun;19(3):271-6. doi: 10.1097/00007691-199706000-00005.
This study was designed to determine the population pharmacokinetic parameters of amikacin in two subpopulations of intensive care unit patients with sepsis and cirrhosis and sepsis without cirrhosis. The authors evaluated the usefulness of the obtained parameters to forecast the serum amikacin concentrations in a validation group of patients with sepsis and cirrhosis when used as a priori distribution in a Bayesian forecaster. The population parameters were estimated by a nonparametric expectation maximization algorithm (NPEM), and the accuracy of the predictions were evaluated through a prediction error analysis. Significant differences (p < 0.05) were found in Vd (0.668 versus 0.470 l/kg) and K (0.0701 versus 0.161 h-1) between subpopulations of patients with and without cirrhosis. The model derived for patients with cirrhosis used as a priori distribution, with and without feedback, was superior to the model derived for patients with sepsis in forecasting amikacin serum concentrations. The results show the relevance of using the specific model for the subgroup with cirrhosis as a priori distribution in a Bayesian forecaster to obtain a nonbiased prediction with an acceptable precision.
本研究旨在确定阿米卡星在两个亚组重症监护病房患者中的群体药代动力学参数，这两个亚组分别为患有脓毒症和肝硬化的患者以及患有脓毒症但无肝硬化的患者。作者评估了所获得的参数在作为贝叶斯预测器的先验分布时，对预测脓毒症和肝硬化患者验证组中血清阿米卡星浓度的有用性。群体参数通过非参数期望最大化算法（NPEM）进行估计，并通过预测误差分析评估预测的准确性。在有肝硬化和无肝硬化的患者亚组之间，发现Vd（0.668对0.470 l/kg）和K（0.0701对0.161 h-1）存在显著差异（p < 0.05）。在预测阿米卡星血清浓度时，将为肝硬化患者推导的模型用作有反馈和无反馈的先验分布，优于为脓毒症患者推导的模型。结果表明，在贝叶斯预测器中使用针对肝硬化亚组的特定模型作为先验分布，以获得具有可接受精度的无偏预测具有重要意义。
