PHARMACODYNAMICS OF NITROGLYCERIN TOLERANCE DEVELOPMENT & RECOVERY

我使用计算机图形学实验室的设施有很多 药代动力学、药效学、扩散和最优控制 模拟。我们目前涉及两个主要领域： 研究：1)最优控制理论应用于给药 表现出耐受性；2)GTN诱导cGMP的定位 耐受性动力学(发展和恢复空间)。在以前的 多年来，我们选择了不同的药代动力学/药效学 (PK/PD)容差模型及其在苏格拉底上的模拟 4-D彩虹升起。我们还运行了一些最优的 关于苏格拉底和伊瑞斯的模拟/计算。最优的 描述给定目标的最优给药方案的曲面 功能最适合用二维和三维曲线图来描述。这项工作是 使用CGL中的交互式图形工作站完成。今年我们 将另一个数学模型添加到公差模型阵列中。 该模型仍在开发中，并以实验为基础 使用LLC-PK1细胞和GTN。我们已经取得了一些实验性的成果 关于该细胞耐受性动态发展的结果 排队。我们正在积极地对这一动力学过程进行数学建模 也在做模拟。CGL资源允许我们完成这两项工作 我们的实验数据的模拟和图形映射，以及 与理论生成的动能空间进行视觉比较。

I use the Computer Graphics Lab facilities for many pharmacokinetic, pharmacodynamic, diffusion, and optimal control simulations. We are currently involved in two major areas of research: 1) Optimal control theory applied to dosing drugs that exhibit tolerance, and 2) the mapping of the GTN-induced cGMP tolerance kinetics (both development and recovery space). In previous years, we have selected different pharmacokinetic/pharmacodynamic (PK/PD) models for tolerance and simulated these models on socrates and the 4-D Irises. We also ran some of our optimal simulations/calculations on both socrates and the Irises. The optimal surfaces describing an optimal dosing regimen for some given objective function can best be described by 2-D and 3-D plots. This work was done using the interactive graphics workstations in CGL. This year we added another mathematical model to the array of tolerance models. This model is still being developed and is based upon experimental work with LLC-PK1 cells and GTN. We have obtained some experimental results regarding the kinetic development of tolerance in this cell line. We are actively mathematically modeling this kinetic process and are doing simulations too. CGL resources allow us to do both the simulations and graphical mapping of our experimental data, as well as visual comparisons to the theoretically generated kinetic space.