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Abstract
1. 1-Hexylcarbamoyl-5-fluoro[6-14C]uracil (14C-HCFU) administered orally to rats, rabbits and dogs at a dose of 10mg/kg was well absorbed and rapidly excreted via the kidney.
2. HCFU was extensively biotransformed, and its six metabolites including two new metabolites were detected in plasma and urine of all three species. Two new metabolites were identified by spectral analysis as 1-(5-oxohexylcarbamoyl)-5-fluorouracil and 1-(5-oxohexylcarbamoyl)-5-fluorouracil.
3. The metabolic pathways of HCFU in the three species involved oxidations and scission of the side-chain with successive degradation of the fluorouracil (FU) released.
4. The two main routes of oxidations of the side chain were ω-oxidation and ω-1-oxidation. Rats metabolized HCFU preferentially by the former reaction, while in rabbits and dogs the latter reaction predominated.