Comparative Toxicity of 5-Fluorouracil (NSC-19893), Ftorafur (NSC-148958),and Fluorodopan (NSC-73754) in Dogs and Monkeys.

摘要

The toxicity of 5-Fluorouracil, Ftorafur,and Fluorodopan was investigated by single and multiple doses in dogs and monkeys. Dogs were 4to 64times more sensitive to the drugs when compared on a mg/sq m basis to monkeys. Lethality in dogs resulted from convulsive seizures. Mild leukopenia was the only other major abnormality. Although monkeys were less sensitive to CNS toxicity,convulsions occurred with high single doses of Ftorafur. More prominent,however,were lesions by all the drugs in rapidly dividing tissues of monkeys. Lesions of bone marrow hypoplasia,lymphoid depletion, catarrhal enteritis,degeneration of intestinal crypt cells,and atrophy of intestinal villi produced clinical and laboratory abnormalities of leukopenia,anemia,thrombocytopenia,secondary infections,and diarrhea. The lesions in monkeys were produced by a mechanism similar to the antitumor effect of the compounds,rather than occurring as a unique sensitivity in dogs to CNS stimulation.