PHARMACODYNAMICS OF NITROGLYCERIN TOLERANCE DEVELOPMENT & RECOVERY

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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.