Metabolic Fate of 1-Hexylcarbamoyl-5-fluorouracil in Rats

Abstract

1. The metabolic fate of a new antitumour agent, 1-hexylcarbamoyl-5-fluoro[6-¹⁴C]uracil (¹⁴C-HCFU) in rats after oral administration was compared with that of 5-fluoro[6-¹⁴C]uracil (¹⁴C-FU).

2. Tissue radioactivity reached a max. 1 to 3 h after administration of ¹⁴C-HCFU and 0.5 h after ¹⁴C-FU.

3. Both drugs were excreted rapidly, mostly in urine. Expired ¹⁴CO² from ¹⁴C-HCFU was significantly less than that from ¹⁴C-FU.

4. Unchanged FU was not detected in plasma 3 h after administration of ¹⁴C-FU, whereas FU was detected in plasma 5 h after ¹⁴C-HCFU. The pyrimidine ring of ¹⁴C-HCFU might be degradated more slowly than that of ¹⁴C-FU.

5. 1-(5-Carboxypentylcarbamoyl)-5-fluorouracil and 1-(3-carboxypropylcar-bamoyl)-5-fluorouracil were identified as the major urinary metabolites of ¹⁴C-HCFU.