PHARMACODYNAMICS OF NITROGLYCERIN TOLERANCE DEVELOPMENT & RECOVERY

我使用计算机图形实验室的设施， 药代动力学、药效学、扩散和最佳控制 模拟 我们目前主要参与两个领域， 研究：1）应用于给药的最优控制理论， 表现出耐受性，和2）GTN诱导的cGMP的映射 耐受性动力学（发育和恢复空间）。 前几 多年来，我们选择了不同的药代动力学/药效学 (PK/PD）模型，并在socrates上对这些模型进行了仿真 还有4D虹膜 我们还进行了一些 对苏格拉底和鸢尾花的模拟/计算。 最优 描述针对某些给定目标的最佳给药方案的曲面 功能可以通过二维和三维图来最好地描述。 这项工作是 使用CGL中的交互式图形工作站完成。 今年我们 在公差模型阵列中添加了另一个数学模型。 该模型仍在开发中，并基于实验 使用LLC-PK 1细胞和GTN。 我们已经获得了一些实验性的 关于该细胞中耐受性的动力学发展的结果 线 我们正在积极地数学建模这个动力学过程 也在做模拟。 CGL的资源使我们能够做到这两点 我们的实验数据的模拟和图形映射，以及 与理论上生成的动力学空间进行视觉比较。

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.