Gueorguieva Ivelina, Ogungbenro Kayode, Graham Gordon, Glatt Sophie, Aarons Leon
Lilly Research Centre, Global PK/PD, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey GU20 6PH, United Kingdom.
Comput Methods Programs Biomed. 2007 Apr;86(1):51-61. doi: 10.1016/j.cmpb.2007.01.004. Epub 2007 Feb 9.
The design of pharmacokinetic and pharmacodynamic experiments concerns a number of issues, among which are the number of observations and the times when they are taken. Often a model is used to describe these data and the pharmacokinetic-pharmacodynamic behavior of a drug. Knowledge of the data analysis model at the design stage is beneficial for collecting patient data for parameter estimation. A number of criteria for model-oriented experiments, which maximize the information content of the data, are available. In this paper we present a program, Popdes, to investigate the D-optimal design of individual and population multivariate response models, such as pharmacokinetic-pharmacodynamic, physiologically based pharmacokinetic, and parent drug and metabolites models. A pre-clinical and clinical pharmacokinetic-pharmacodynamic model describing the concentration-time profile and effect of an oncology compound in development is used for illustration.
药代动力学和药效学实验的设计涉及许多问题，其中包括观察次数及其采集时间。通常会使用一个模型来描述这些数据以及药物的药代动力学-药效学行为。在设计阶段了解数据分析模型有助于收集用于参数估计的患者数据。有一些面向模型的实验标准，可使数据的信息含量最大化。在本文中，我们展示了一个程序Popdes，用于研究个体和群体多变量反应模型的D最优设计，如药代动力学-药效学、基于生理的药代动力学以及母体药物和代谢物模型。文中以一个描述正在研发的一种肿瘤化合物的浓度-时间曲线和效应的临床前及临床药代动力学-药效学模型为例进行说明。
