Abstract
A study of the metabolic degradation of 5-fluorouracil has been carried out in mice and human cancer patients. 5-Fluoroorotic acid is not significantly degraded by mice. The first steps of 5-fluorouracil degradation, the conversion to dihydrofluorouracil and α-fluoro-β-ureidopropionic acid, are exactly analogous to those of uracil. In human subjects there is extensive conversion of FU to urea. Most normal tissues, except spleen, degrade FU in vivo. The liver is probably the main site of degradation, and studies with high-speed supernatant fractions have been carried out. Two mouse tumours have been shown to be incapable of degrading the drug. In human beings there is more extensive catabolism when the drug is administered orally than by intravenous injection. There is a higher concentration of radioactivity in a human malignant carcinoma and intestinal mucosa than in the normal tissues and a benign fibro-adenoma. The presence of α-fluoro-β-guanidopropionic acid as a metabolite of 5-fluorouracil has been suggested.
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