Studies on the metabolic fate of 5-fluorouracil in the oral administration

Abstract

The metabolic fate of 5-fluorouracil (5-FU) after its oral administration was studied in comparison with its intravenous administration using normal rats and solid Sarcoma-180 bearing mice, and results are summarized as follows : 1) When 5-fluorouraci1[2-14C] was given orally to rats, it was readily absorbed from the small intestine and the radioactivity was detected in various tissues and organs. Particularly, a higher radioactivity was counted in the small intestine, stomach, liver, and pancreas after orally than intravenous administration in rats. 2) The rapid rate of the metabolic degradation of 5-fluorouracil was found by both routes. Within 4 hr after oral or intravenous administration, about 80% of the total radioactivity was excreted into the expiration and urine. 3) Slightly larger radioactivity in the expiratory CO2 and high concentration of the degradation products, such as urea and 2-fluoro-3-ureidopropionate, in the urine were observed after oral administration in than after intravenous administration in rats. 4) The blood and tissue levels of the degradative products in the tumor-bearing mice were found a little higher after the oral than intravenous administration. 5) Orally administered 5-fluorouraci1 seemed to be catabolized more extensively than that administered intravenously in both mice and rats. However, in both routes excessive dose of 5-fluorotracil produced a different excretion pattern and high urinary levels of 5-fluorouracil.