Effect of coadministration of uracil on the toxicity of tegafur.
The cardiotoxic and neurotoxic effects of tegafur, an anticancer agent, were compared with those of uracil plus tegafur (4:1 mol/mol) in mice, rats, rabbits, cats and dogs. Uracil plus tegafur was shown to be less toxic than the drug alone in all the species, and uracil was found to decrease the toxicity of tegafur. alpha-Fluoro-beta-alanine, a catabolic metabolite of the drug, had toxic effects similar to tegafur. The results suggest that administration of uracil with tegafur prevents the side effects of the drug on the heart and CNS by inhibiting the degradation of 5-fluorouracil.
D000818:Animals; D002415:Cats; D004285:Dogs; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives*; D006331:Heart Diseases / Q000139:chemically induced; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009422:Nervous System Diseases / Q000139:chemically induced; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D005641:Tegafur / Q000037:antagonists & inhibitors* / Q000633:toxicity; D014498:Uracil / Q000494:pharmacology*; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000633:toxicity
D015091:beta-Alanine; D005641:Tegafur; C032348:alpha-fluoro-beta-alanine; D014498:Uracil; D005472:Fluorouracil