使用贝叶斯药代动力学模型预测新生儿和婴儿庆大霉素浓度。

K A Rodvold, C A Gentry, G S Plank, D M Kraus, E Nickel, J R Gross
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引用次数: 8

摘要

本研究回顾性地描述了庆大霉素在新生儿和婴幼儿中基于人群的药代动力学参数,并在贝叶斯预测程序中评估了这些参数的预测性能。使用单室开放输注模型和非线性最小二乘回归分析,从19例新生儿和婴儿的血清浓度-时间数据确定总体参数估计。采用单变量和多元逐步线性回归分析确定人口学特征与庆大霉素药动学参数之间的显著关系。肌酐清除率和出生后年龄是体重标准化庆大霉素清除率的最显著预测因子(模型r2 = 0.86)。患者特征与基于人群的参数之间的关系被纳入单室贝叶斯预测模型。第二组17名接受35个疗程庆大霉素治疗的新生儿和婴儿被用来评估基于人群的参数和贝叶斯预测模型的预测性能。总体参数提供了准确的预测稳态庆大霉素浓度在多个疗程的治疗在同一患者。一旦一组稳定的庆大霉素峰值和谷浓度可用,贝叶斯预测进一步最小化平均预测误差(偏差)(峰值浓度:-0.062 vs -0.273 mg/l;谷浓度:-0.006 vs. -0.161 mg/l)。两组参数的平均绝对误差(精度)相似。观察到的总体参数和贝叶斯预测的准确性表明,对新生儿和婴儿的血清庆大霉素浓度监测可以保持在最低限度。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prediction of gentamicin concentrations in neonates and infants using a Bayesian pharmacokinetic model.

This study retrospectively characterized population-based pharmacokinetic parameters for gentamicin in neonates and young infants, and evaluated the predictive performance of these parameters in a Bayesian forecasting program. Population parameter estimates were determined from the serum concentration-time data of 19 neonates and infants using a one-compartment open infusion model and nonlinear least-squares regression analysis. Univariate and multiple stepwise linear regression analyses were used to determine significant relationships between demographic characteristics and gentamicin pharmacokinetic parameters. Creatinine clearance and postnatal age were the most significant predictors of weight-standardized gentamicin clearance (model r2 = 0.86). The relationships between patient characteristics and population-based parameters were incorporated into the one-compartment Bayesian forecasting model. A second group of 17 neonates and infants receiving 35 courses of gentamicin therapy were used to evaluate the predictive performance of the population-based parameters and a Bayesian forecasting model. The population parameters provided accurate prediction of steady state gentamicin concentrations throughout multiple courses of therapy within the same patient. Bayesian forecasting further minimized the mean prediction error (bias) once a set of steady state peak and trough serum gentamicin concentrations became available (peak concentrations: -0.062 vs. -0.273 mg/l; trough concentrations: -0.006 vs. -0.161 mg/l). The mean absolute error (accuracy) was similar for the two sets of parameters. The observed accuracy of both the population parameters and Bayesian forecasting suggests that monitoring of serum gentamicin concentrations can be kept to minimum in neonates and infants.

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