Metabolism, antitumor activity, and acute toxicity of 5-fluoro-1,3-bis(tetrahydro-2-furanyl)-2,4-pyrimidinedione by oral administration to animals.

Abstract

The metabolism, antitumor activity, and acute toxicity of 5-fluoro-1,3-bis-(tetrahydro-2-furanyl)-2,4-pyrimidinedione (FD-1) were investigated in animals, compared with 5-fluoro-1-(tetrahydro-2-furanyl)-2,4-pyrimidinedione (FT). It was found that after oral administration of FD-1, the level of 5-fluorouracil (5-FU) was maintained higher and longer than after administration of FT, and that a large amount of 5-FU was released from FD-1 by liver microsomal drug-metabolizing enzymes or spontaneous hydrolysis via 5-fluoro-3-(tetrahydro-2-furanyl)-2,4-pyrimidinedione (3-FT) and FT. FD-1 had a significant activity against the solid form of Ehrlich carcinoma, sarcoma-180, hepatoma AH130, Yoshida sarcoma, Walker carcinosarcoma-256, and leukemia L1210 and P388, but not the ascitic forms, and it produced greater inhibition of tumor growth than FT. The acute toxicity of FD-1 was less than that of FT.

• Authors: S Fujii, Y Nakamura, S Takeda, K Morita, T Sato, T Marunaka, Y Kawaguchi, N Unemi
• Journal: Gan (Gan) Vol. 71 Issue 1 Pg. 30-44 (Feb 1980) ISSN: 0016-450X [Print] Japan
• PMID: 6769737 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Tegafur
• FD 1
• Fluorouracil

Topics

• Administration, Oral
• Animals
• Antineoplastic Agents (metabolism, pharmacology, toxicity)
• Biotransformation
• Chemical Phenomena
• Chemistry
• Fluorouracil (analogs & derivatives, blood, urine)
• In Vitro Techniques
• Male
• Mass Spectrometry
• Microsomes, Liver (metabolism)
• Rats
• Tegafur (analogs & derivatives, metabolism, pharmacology, toxicity)
• Tissue Distribution