Comparative studies on the metabolism of 2-(tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil.
5=Fluorouracil inhibited DNA synthesis markedly using various DNA precursors such as deoxyuridine, orotic acid, uracil, and uridine except for thymidine. 2-(Tetrahydrofury)-5-fluorouracil (FT-207) did not inhibit DNA synthesis with any of the precursors tested. The metabolisms of 5-fluorouracil and FT-207 in mice and rats were studied. When administered intravenously 5-fluorouracil was rapidly degraded to fluoro-beta-alanine in both mice and rats, while at most 70% of FT-207 was slowly degraded after a prolonged period. The metabolites of FT-207 were found to be 5-fluorouracil and fluoro-beta-alanine in both species of animals. In vitro degradation of FT-207 into 5-fluorouracil was observed mainly in the microsomal fraction in the presence of NADPH. This result suggested that microsomal electron-transport system was concerned with the degradation of FT-207.
D000409:Alanine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism*; D009694:Nucleic Acid Precursors / Q000378:metabolism; D051381:Rats; D005641:Tegafur / Q000378:metabolism* / Q000494:pharmacology; D014018:Tissue Distribution
D004273:DNA, Neoplasm; D009694:Nucleic Acid Precursors; D005641:Tegafur; D009249:NADP; D000409:Alanine; D005472:Fluorouracil