Metabolic fate on 1-hexylcarbamoyl-5-fluorouracil and 5-fluorouracil in mice bearing ascites sarcoma 180.
Patterns of metabolism and disposition in plasma of tumor-bearing mice after oral administration of [6(-14)C]1-hexylcarbamoyl-5-fluorouracil ([6(-14)C]HCFU) resembled those in plasma of normal mice, but elimination of [6(-14)C]HCFU and 5-fluorouracil (FUra) was slower in tumor-bearing mice. The level of 1-(5-hydroxyhexylcarbamoyl)-5-fluorouracil (HHCFU) was lower in tumor-bearing mice. Also detected in plasma were [6(-14)C]HCFU, HHCFU, 1-(3-carboxypropylcarbamoyl)-5-fluorouracil, FUra, 5,6-dihydro-5-fluorouracil, and alpha-fluoro-beta-alanine. FUra originating from [6(-14)C]HCFU was retained over 6 hours, whereas intact FUra after [6(-14)C]FUra administration disappeared within 2 hours. The pattern of metabolism in ascitic fluid was similar to that in plasma after [6(-14)C]HCFU and [6(-14)C]FUra administration, but FUra was retained for a longer period in ascitic fluid. In sarcoma 180 cells, the maximum concentration of total radioactivity was observed 1 or 2 hours after [6(-14)C]FUra or [6(-14)C]HCFU administration, respectively, and the level of intact HCFU was very low. The principal metabolites were nucleotides that were maintained for a long period after administration of both compounds. The pattern of other metabolites after [6(-14)C]HCFU administration was also similar to that after [6(-14)C]FUra administration.[1]References
- Metabolic fate on 1-hexylcarbamoyl-5-fluorouracil and 5-fluorouracil in mice bearing ascites sarcoma 180. Iigo, M., Kuretani, K., Hoshi, A. J. Natl. Cancer Inst. (1981) [Pubmed]
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