Animal-to-Human Extrapolation Using Compartmental Models
Interim rept. Oct 1989-Apr 1990
SCHOOL OF AEROSPACE MEDICINE BROOKS AFB TX
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We have been studying how to use compartmental models to reliably extrapolate toxicological experiment results from one animal species to another with the ultimate goal of useful extrapolation to man. We have taken as the fundamental core of our analysis the physically necessary equations of the form VaCdt Qa-v. These equations are not a complete set since they are insufficient to provide estimation of venous arterial or tissue concentrations with time. Therefore, the mass balance equations must ne augmented with additional phenomenological relations to permit the desired calculations. Many investigators use the venous exit condition. While it is clear how to extrapolate the mass balance equations from one sized animal to another for from one species to another. it is not clear how to extrapolate the venous exit condition. In this research we have evaluated the venous exit condition by comparing it with approximate analyses of perfusion and substance diffusion in the tissue.