Metabolism, antitumor activity, and acute toxicity of 5-fluoro-1,3-bis(tetrahydro-2-furanyl)-2,4-pyrimidinedione by oral administration to animals.
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.
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D005641:Tegafur / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D005641:Tegafur; C016882:FD 1; D005472:Fluorouracil