NITROGLYCERIN TOLERANCE DEVELOPMENT & RECOVERY IN LLC PK1 CELLS

硝酸甘油耐受性的发展

• 批准号: 6119268
• 负责人: JIM UCHIZONO
• 金额: $ 0.54万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6119268
• 关键词: bioengineering /biomedical engineering; biomaterials; biomedical resource; statistics /biometry

I use the Computer Graphics Laboratory 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). We have selected different pharmacokinetic/pharmacodynamic (PK/PD) models for tolerance and simulated these models. We have also run optimal simulations/calculations. 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 is done using the interactive graphics workstations in CGL. Now we are adding 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 comparisions to the theoretically generated kinetic space.

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）最优控制理论应用于给药， 表现出耐受性和2）GTN诱导的cGMP耐受性的作图 动力学（发展和恢复空间）。 我们选择 耐受性的不同药代动力学/药效学（PK/PD）模型 并模拟了这些模型。 我们还运行了最佳 模拟/计算。 描述最优曲面的最优曲面 对于某些给定的目标函数， 通过二维和三维图。 这项工作是使用交互式 CGL中的图形工作站。 现在我们又增加了一个数学 模型到公差模型阵列。 这一模式目前仍在 开发并基于LLC-PK 1细胞的实验工作， GTN。 我们已经获得了一些关于动力学的实验结果 在该细胞系中产生耐受性。 我们正在积极 数学建模这个动力学过程， 也 CGL资源允许我们进行模拟和图形化 我们的实验数据的映射，以及视觉比较， 理论上产生的动能空间