Heatherington A C, Vicini P, Golde H
Resource Facility for Population Kinetics, Department of Bioengineering, University of Washington, Box 352255, Seattle, Washington 98195-2255, USA.
J Pharm Sci. 1998 Oct;87(10):1255-63. doi: 10.1021/js9603562.
This paper presents a detailed comparison of the kinetic analysis software packages SAAM II and PCNonlin/WinNonlin, based on benchmark modeling problems reported in "Pharmacokinetic andPharmacodynamic Data Analysis: Concepts and Applications" (Gabrielsson and Weiner, 1994) and seven additional models. For each model, both software packages were presented with identical implementations. Models were initially executed in PCNonlin or WinNonlin and automated comparisons with SAAM II made using Microsoft Test. Models investigated included one- and multicompartment models with nonlinearities, multiple inputs and samples, multiple simultaneous experiments, and linear equations. Maximum number of compartments, data sets, and parameters were 9, 5, and 10, respectively. We compared 88 different models, many of them in different configurations, e.g., different weighting schemes or different parameter limits. The total number of attempted comparisons between SAAM II and PCNonlin was 161, of which 142 executed without problems. Parameter estimates, their precision (standard errors), and model predictions were compared; a difference of 1% or less was considered "agreement". Observed differences, mainly in parameter standard errors, can be accounted for in terms of different optimization algorithms, convergence criteria, and individual capabilities. In general, there was good agreement (<1% difference) between SAAM II and PCNonlin in terms of parameter estimates and model predictions. However, due to differences in the optimization procedure, parameter standard errors showed considerable differences. Additionally, there were differences when multiple data sets were fitted, indicating the importance of different fitting procedures for interpreting multiple kinetic data sets. The full results of the comparison and the model files in SAAM II and PCNonlin/WinNonlin formats are available from the authors.
本文基于《药代动力学和药效学数据分析：概念与应用》（加布里埃尔松和维纳，1994年）中报告的基准建模问题以及另外七个模型，对动力学分析软件包SAAM II和PCNonlin/WinNonlin进行了详细比较。对于每个模型，两个软件包都采用相同的实现方式。模型最初在PCNonlin或WinNonlin中执行，并使用Microsoft Test与SAAM II进行自动比较。研究的模型包括具有非线性、多个输入和样本、多个同步实验以及线性方程的单室和多室模型。隔室、数据集和参数的最大数量分别为9、5和10。我们比较了88个不同的模型，其中许多模型具有不同的配置，例如不同的加权方案或不同的参数限制。SAAM II和PCNonlin之间尝试比较的总数为161次，其中142次顺利执行。对参数估计值、其精度（标准误差）和模型预测进行了比较；差异在1%或以下被视为“一致”。观察到的差异主要体现在参数标准误差方面，可以从不同的优化算法、收敛标准和各自的功能方面进行解释。总体而言，SAAM II和PCNonlin在参数估计和模型预测方面具有良好的一致性（差异<1%）。然而，由于优化过程的差异，参数标准误差显示出相当大的差异。此外，在拟合多个数据集时也存在差异，这表明不同的拟合程序对于解释多个动力学数据集的重要性。比较的完整结果以及SAAM II和PCNonlin/WinNonlin格式的模型文件可从作者处获取。
