Administration Of 5FU Research Articles

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.

Distribution of 1-hexylcarbamoyl-5-fluorouracil and 5-fluorouracil by oral administration in mice.

The distribution of 1-hexylcarbamoyl-5-fluorouracil-6-14C (HCFU) and 5-fluorouracil-6-14C (5FU) was studied in mice following a single oral administration. When HCFU and 5FU were given orally to mice, they were readily absorbed from the gastrointestinal tract and the radioactivity was detected in various tissues and organs. Highest radioactivity after administration of HCFU was shown in the liver, kidneys, stomach wall and plasma, followed by the lungs, and adrenals. On the other hand, highest radioactivity after administration of 5FU was exhibited in the liver, myocardium, lungs, pancreas, spleen, kidneys, adrenals and gastro-intestinal wall. Distribution pattern and disppearance of HCFU were similar to those of 5FU. Marked difference in the distribution between HCFU and 5FU was detected only in the gastro-intestinal wall, namely, HCFU was retained for a long period in the stomach wall while 5FU did in the intestinal wall.