Nonlinear pharmacokinetic models for 5-fluorouracil in man: intravenous and intraperitoneal routes

A two-compartment physiologic pharmacokinetic model has been developed for 5-fluorouracil (5FU). This model, which incorporates saturable whole body clearance, satisfactorily predicts disappearance kinetics after an intravenous bolus and steady-state levels during constant intravenous infusions. A half-saturating concentration (KM) of 15 microM was determined by comparison of model simulations with literature data. Both hepatic and extrahepatic elimination can be inferred for 5FU, but the exact anatomic or compartmental location of the clearance cannot be determined from the available clinical data. The effect of venous and arterial plasma sampling is discussed. This model has been extended to include intraperitoneal and oral administration of 5FU by the addition of peritoneal fluid and liver compartments.