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

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Abstract
A 2-compartment physiologic [human] pharmacokinetic model was developed for [the antineoplastic drug] 5-fluorouracil (5FU). This model, which incorporates saturable whole body clearance, satisfactorily predicts disappearance kinetics after an i.v. bolus and steady-state levels during constant i.v. infusions. A half-saturating concentration (Km) of 15 .mu.M was determined by comparison of model simulations with literature data. Hepatic and extrahepatic elimination can be inferred for 5FU; 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 was extended to include i.p. and oral administration of 5FU by the addition of peritoneal fluid and liver compartments.