WHOLE BODY DISTRIBUTION & PHARMACOKINETIC MODELS

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A central target for the Simulation Resource is the provision of tools for understanding the kinetics of blood-tissue exchange. Of particular interest are outflow indicator dilution techniques, residue techniques applied to positron emission tomography (PET), magnetic resonance imaging (MRI), & X-ray computed tomography (CT), the characterization of carrier-mediated transport and receptor kinetics, and high resolution pharmacokinetics. While in some experimental settings these can be examined in open (i.e., non-recirculating) systems, many experiments are performed in intact subjects, and their analysis requires the use of whole-body, recirculating models. The goal of this project is to develop a set of models for tracer transport and exchange that are sufficiently realistic to accurately account for observed anatomic and physiologic data for the behavior of a wide range of unmetabolized and metabolized substrates, ions, and hormones in the whole body. These models will be coded in a manner that the computation is rapid enough that they can be used for model fitting to data and parameter estimation on workstations rather than supercomputers. They will also be constructed so that they can be reduced to compartmental forms and can, thus, allow comparisons between physiologically realistic distributed models and traditional compartmental analysis.