Identifiability and indistinguishability of nonlinear pharmacokinetic models
Identifiability and indistinguishability of nonlinear pharmacokinetic models
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DOI：
10.1007/bf02353330
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发表时间：
1994-06
期刊：
影响因子：
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通讯作者：
K. Godfrey;M. J. Chapman;S. Vajda
中科院分区：
文献类型：
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作者：
K. Godfrey;M. J. Chapman;S. Vajda
分析了药代动力学中三个重要的非线性模型结构，以确定如果有完美的输入输出数据，是否可以推导出未知的、独立的模型参数。这就是可识别性的问题。该方法基于局部状态同构定理。在某些情况下，建模者可能在几种模型结构之间犹豫不决，然后确定是否可以将不同的模型结构与完美的输入-输出数据区分开来。这就是模型不可区分性的问题。所使用的技术，同样基于局部状态同构定理，与本杂志先前描述的线性系统的相似变换方法相似。对三个具有一个线性和一个非线性（Michaelis-Menten）消除路径的两室例子进行了分析。在每个模型中，基于生理和其他原因，对于其中一个消除途径的精确位置（中央隔室或外周隔室）都存在一些不确定性。
Three nonlinear model structures of interest in pharmacokinetics are analyzed to determine whether the unknown, independent, model parameters can be deduced if perfect input-output data were available. This is the problem of identifiability. The method used is based on the local state isomorphism theorem. In certain circumstances, the modeler may be undecided between several model structures and it is then of interest to determine whether different model structures can be distinguished from perfect input-output data. This is the problem of model indistinguishability. The technique used, again based on the local state isomorphism theorem, parallels the similarity transformation approach for linear systems described previously in this journal. The analysis is performed on three two-compartment examples having one linear and one nonlinear (Michaelis-Menten) elimination pathway. In each model there is, on physiological and other grounds, some uncertainty over the precise location (central compartment or peripheral compartment) of one of the elimination pathways.