PHARMACODYNAMICS OF NITROGLYCERIN TOLERANCE DEVELOPMENT & RECOVERY

我使用计算机图形实验室的设施进行了许多工作 药代动力学、药效学、扩散和最佳控制 模拟。 目前我们主要涉足两大领域 研究：1）最优控制理论应用于药物剂量 表现出耐受性，2) GTN 诱导的 cGMP 的定位 耐受动力学（发育和恢复空间）。 在之前的 多年来，我们选择了不同的药代动力学/药效学 (PK/PD) 耐受性模型并在苏格拉底上模拟这些模型 和 4-D 鸢尾花。 我们还运行了一些最佳的 对苏格拉底和鸢尾花的模拟/计算。 最优的 描述某些给定目标的最佳给药方案的表面 函数可以通过 2-D 和 3-D 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 在公差模型数组中添加了另一个数学模型。 该模型仍在开发中，并且基于实验 与 LLC-PK1 细胞和 GTN 一起使用。 我们已经获得了一些实验结果 关于该细胞耐受性动力学发展的结果 线。 我们正在积极对这一动力学过程进行数学建模 并且也在做模拟。 CGL 资源使我们能够做到 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的视觉比较。

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.