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

Abstract

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 ω-1 oxidation.

3. FU was detected in plasma 180min after oral administration of ¹⁴C-HCFU, whereas unchanged FU disappeared within 60min 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.