Metabolic fate of 1-hexylcarbamoyl-5-fluorouracil after oral administration in mice.

1. The metabolic fate of a new antitumour agent, 1-hexylcarbamoyl-5-fluoro[6-14C]uracil (14C-HCFU) was compared with that of 5-fluoro[6-14C]uracil (14C-FU) after oral administration to mice. 2. 1-(5-Hydroxyhexylcarbamoyl)-5-fluorouracil (5-hydroxy-HCFU) and 1-(5-oxohexylcarbamoyl)-5-fluorouracil (5-keto-HCFU) were found as major intermediate metabolites of 14C-HCFU and were produced by omega-1 oxidation. 3. FU was detected in plasma 180 min after oral administration of 14C-HCFU, whereas unchanged FU disappeared within 60 min after 14C-FU. 4. 14C-HCFU and resulting FU were retained in tissues for a long period after oral administration, while administered 14C-FU was rapidly degraded.