A multi-compartment pharmacokinetic model of 5-fluorouracil and dihydrofluorouracil

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Osunbiyi, Olusoji
University of Lethbridge. Faculty of Arts and Science
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Lethbridge, Alta. : University of Lethbridge, Dept. of Physics and Astronomy
5-Fluorouracil (5-FU) is extensively biotransformed to dihydrofluorouracil (DHFU) by the dihydropyrimidine dehydrogenase enzyme (DPD) that catalyzes the reduction of uracil and thymine. This research involves the development of intensive quantitative compartment models that predict the time course of 5-FU and DHFU in the body using the Runge-Kutta fourth order method. The parameters within our system of nonlinear differential equations were determined by fitting the models to the clinical data. We showed that the one-compartment model was insufficient to describe the kinetics of 5-FU and that a minimum of two compartments is needed. The area under the curve (AUC), maximum concentration ($C_{max}$), and half-life ($t_{1/2}$) were obtained from the theoretical solutions to our models. Further work was done on how age and gender influence the drug's interaction with the body. It was determined that age reduces the rate of elimination and women are more prone to toxic effects.
Pharmacokinetics , Pharmacology , Chemotherapy , Cancer -- Chemotherapy , Pharmacokinetics -- Mathematical models , Cancer -- Treatment