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

Abstract

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 x kg-1 x hr-1, corresponding to a dose of 15 mg x kg-1 x 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%.

Different Intravenous Administration Techniques for 5-Fluorouracil Pharmacokinetics and Pharmacodynamic Effects

“…The hepatic circulation is important for 5-FU elimination, but plasma clearance rate equals or exceeds liver circulation in Received 22 some patients. Extensive drug elimination has been found in the cardiopulmonary circulation and in the splanchnic area (4, 5). The plasma clearance equals or exceeds cardiac output at low-drug concentrations.…”

“…Bolus 5-fluorouracil push injection rather than a short-time infusion appears to be the more efficient administration technique. 5-Flurorouracil (5-FU) remains one of the most widely used agents in pharmacotheraphy against breast and colorectal cancer (1). Basic research in 5-FU anabolism, catabolism, excretion and cytotoxicity has provided a theoretical background for its usefulness ( 2 ) .…”

Pharmacokinetics of 5‐fluorouracil in mutant Nagase analbuminemic rats: faster metabolism of 5‐fluorouracil via CYP1A

“…The negligible GI 24 h, less than 0.264%, was not due to chemical and enzymatic degradation of 5-fluorouracil in the gastric fluid as mentioned in the stability studies. Moreover, the negligible biliary excretion of 5-fluorouracil has been also reported in rats (the amounts of 5-fluorouracil in bile negligibly contribute to the elimination of the total drugs [31]), two cancer patients with extended biliary catheters (2-3% of the administered total radioactivity were excreted in bile [32]) and dogs (negligible amounts of 5-fluorouracil were excreted in the bile [33]). The aforementioned data suggest that the Cl nr of 5-fluorouracil listed in Table 1 could represent the metabolic clearance of the drug.…”

Effects of dosage and infusion time on the incorporation of 5‐fluorouracil into DNA and RNA of normal tissues and an adenocarcinoma transplanted to rat liver

“…firmed that the hepatic artery is the optimal route for ~i~~~ metastases from colorectal cancer represent a drug administration in liver malignancies [5,7,8]. Differmajor clinical problem.…”