Regional and systemic serum concentrations of 5-fluorouracil after portal and intravenous infusion: An experimental study in dogs

The serum and urinary concentrations of 5-FU after continuous portal and jugular infusion have been followed by means of a highly sensitive microbiological assay method. Our data indicate that more than 90% of 5-FU was eliminated in the liver after continuous portal infusion of 0.625 mg × kg^–1× hr^–1,corresponding to a dose of 15 mg × kg^–1 ×24 hr^–1.Negligible amounts of intact 5-FU were excreted into the bile, and the urinary excretion was only a few percent of the amount infused. The arterial concentration was on average tenfold higher during the continuous jugular infusion than after the continuous portal infusion, indicating that the route of administration has a pronounced effect on the disposition of 5-FU. Twenty-three percent of the jugular dose reached the liver; 77% was degraded by extrahepatic metabolism. Of these, degradation in the prehepatic splanchnic area accounted for 15%.This research was supported by the Swedish Cancer Society (Projects No. 512-B74-04X and 512-B75-05X).