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神经网络预测庆大霉素的峰浓度和谷浓度。

Neural network predicted peak and trough gentamicin concentrations.

作者信息

Brier M E, Zurada J M, Aronoff G R

机构信息

Department of Medicine, University of Louisville, Kentucky, USA.

出版信息

Pharm Res. 1995 Mar;12(3):406-12. doi: 10.1023/a:1016260720218.

Abstract

Predictions of steady state peak and trough serum gentamicin concentrations were compared between a traditional population kinetic method using the computer program NONMEM to an empirical approach using neural networks. Predictions were made in 111 patients with peak concentrations between 2.5 and 6.0 micrograms/ml using the patient factors age, height, weight, dose, dose interval, body surface area, serum creatinine, and creatinine clearance. Predictions were also made on 33 observations that were outside the 2.5 and 6.0 micrograms/ml range. Neural networks made peak serum concentration predictions within the 2.5-6.0 micrograms/ml range with statistically less bias and comparable precision with paired NONMEM predictions. Trough serum concentration predictions were similar using both neural networks and NONMEM. The prediction error for peak serum concentrations averaged 16.5% for the neural networks and 18.6% for NONMEM. Average prediction errors for serum trough concentrations were 48.3% for neural networks and 59.0% for NONMEM. NONMEM provided numerically more precise and less biased predictions when extrapolating outside the 2.5 and 6.0 micrograms/ml range. The observed peak serum concentration distribution was multimodal and the neural network reproduced this distribution with less difference between the actual distribution and the predicted distribution than NONMEM. It is concluded that neural networks can predict serum drug concentrations of gentamicin. Neural networks may be useful in predicting the clinical pharmacokinetics of drugs.

摘要

将使用计算机程序NONMEM的传统群体动力学方法与使用神经网络的经验方法对稳态峰谷血清庆大霉素浓度的预测结果进行了比较。利用患者的年龄、身高、体重、剂量、给药间隔、体表面积、血清肌酐和肌酐清除率等因素,对111例峰浓度在2.5至6.0微克/毫升之间的患者进行了预测。还对33例超出2.5至6.0微克/毫升范围的观察结果进行了预测。神经网络对2.5至6.0微克/毫升范围内的血清峰浓度预测在统计学上偏差更小,与配对的NONMEM预测精度相当。使用神经网络和NONMEM对谷血清浓度的预测结果相似。神经网络对血清峰浓度的预测误差平均为16.5%,NONMEM为18.6%。神经网络对血清谷浓度的平均预测误差为48.3%,NONMEM为59.0%。当在2.5至6.0微克/毫升范围之外进行外推时,NONMEM在数值上提供了更精确且偏差更小的预测。观察到的血清峰浓度分布是多峰的,并且神经网络再现了这种分布,实际分布与预测分布之间的差异比NONMEM小。得出的结论是,神经网络可以预测庆大霉素的血清药物浓度。神经网络可能有助于预测药物的临床药代动力学。

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