Levitt David G
Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN 55455, USA.
BMC Res Notes. 2009 Aug 5;2:158. doi: 10.1186/1756-0500-2-158.
Physiologically based pharmacokinetics (PBPK) uses a realistic organ model to describe drug kinetics. The blood-tissue exchange of each organ is characterized by its volume, perfusion, metabolism, capillary permeability and blood/tissue partition coefficient. PBPK applications require both sophisticated mathematical modeling software and a reliable complete set of physiological parameters. Currently there are no software packages available that combine ease of use with the versatility that is required of a general PBPK program.
The program is written in Java and is available for free download at http://www.pkquest.com/. Included in the download is a detailed tutorial that discusses the pharmacokinetics of 6 solutes (D2O, amoxicillin, desflurane, propofol, ethanol and thiopental) illustrated using experimental human pharmacokinetic data. The complete PBPK description for each solute is stored in Excel spreadsheets that are included in the download. The main features of the program are: 1) Intuitive and versatile interactive interface; 2) Absolute and semi-logarithmic graphical output; 3) Pre-programmed optimized human parameter data set (but, arbitrary values can be input); 4) Time dependent changes in the PBPK parameters; 5) Non-linear parameter optimization; 6) Unique approach to determine the oral "first pass metabolism" of non-linear solutes (e.g. ethanol); 7) Pulmonary perfusion/ventilation heterogeneity for volatile solutes; 8) Input and output of Excel spreadsheet data; 9) Antecubital vein sampling.
PKQuest_Java is a free, easy to use, interactive PBPK software routine. The user can either directly use the pre-programmed optimized human or rat data set, or enter an arbitrary data set. It is designed so that drugs that are classified as "extracellular" or "highly fat soluble" do not require information about tissue/blood partition coefficients and can be modeled by a minimum of user input parameters. PKQuest_Java, along with the included tutorial, could be used as the basis of an interactive, on-line, pharmacokinetic course.
基于生理的药代动力学（PBPK）使用逼真的器官模型来描述药物动力学。每个器官的血液-组织交换由其体积、灌注、代谢、毛细血管通透性和血液/组织分配系数来表征。PBPK的应用既需要复杂的数学建模软件，也需要一套可靠完整的生理参数。目前没有既易于使用又具备通用PBPK程序所需多功能性的软件包。
PKQuest_Java是一个免费、易于使用的交互式PBPK软件程序。用户既可以直接使用预编程的优化人体或大鼠数据集，也可以输入任意数据集。其设计使得被归类为“细胞外”或“高脂溶性”的药物不需要组织/血液分配系数信息，并且可以用最少的用户输入参数进行建模。PKQuest_Java以及所包含的教程可作为交互式在线药代动力学课程的基础。
