Collections > Master's Papers > Gillings School of Public Health > 5-Fluorouracil: A Metabolism Model of the Rat Liver

A metabolism model of 5-fluorouracil (FU), a nucleotide synthesis interference chemical, was created based on rat liver metabolism data. The model of the adult rat predicted that 0.1% of the original FU dose will become 5-fluorodeoxyuridine monophosphate (FdUMP), a thymidine synthetase inhibiting metabolite. Model parameters were derived from enzyme activity information. It can be concluded from the results of this model that a very small percentage of the initial FU dose actually becomes the metabolite FdUMP. This is the first model to focus on the anabolism portion of the overall metabolism of FU. The overall goal of the research program is to help in the develop of a pharmacokinetic, biologically based dose-response model of FU to test the feasibility for modeling nucleotide synthesis inhibitors. The rat liver metabolism is merely one part of the modeling picture which is needed to look at developmental effects due to interference with nucleotide synthesis, but it is a place to begin.