Grey-box pharmacokinetic/pharmacodynamic (PK/PD) modelling is presented as a promising way of modelling PK/PD systems. The concept behind grey-box modelling is based on combining physiological knowledge along with information from data in the estimation of model parameters. Grey-box modelling consists of using stochastic differential equations (SDEs) where the stochastic term in the differential equations represents unknown or incorrectly modelled dynamics of the system. The methodology behind the grey-box PK/PD modelling framework for systematic model improvement is illustrated using simulated data and furthermore applied to Bergman's minimal model of glucose kinetics using clinical data from an intravenous glucose tolerance test (IVGTT). The grey-box estimates of the stochastic system noise parameters indicate that the glucose minimal model is too simple and should preferably be revised in order to describe the complicated in vivo system of insulin and glucose following an IVGTT.

中文翻译：

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药代动力学/药效动力学系统的灰色框建模。

提出了灰盒药代动力学/药效学（PK / PD）建模，作为对PK / PD系统建模的一种有前途的方法。灰匣子建模背后的概念是基于将生理知识与来自数据的信息结合在一起，用于估计模型参数。灰盒建模包括使用随机微分方程（SDE），其中微分方程中的随机项表示系统动力学的未知或建模错误。使用模拟数据说明了灰箱PK / PD建模框架背后用于系统模型改进的方法，并使用静脉葡萄糖耐量试验（IVGTT）的临床数据将其应用于Bergman的葡萄糖动力学最小模型。