Abstract
The correlations of the 5‐fluorouracil (5‐FU) level in the plasma and the duration of continuous 5‐FU infusion with the antitumor activity of 5‐FU on Yoshida sarcomas in rats were examined. The circadian variation in the plasma level of 5‐FU during continuous infusion was prevented by treatment with 3‐cyano‐2,6‐dihydroxypyridine (CNDP), which strongly inhibits 5‐FU degradation. On continuous venous infusion of 2 to 30 mg/kg of 5‐FU over 24 h with CNDP at a molar ratio of 1:10 into normal rats, the 5‐FU level in the blood was linearly proportional to the dose of 5‐FU. The optimum schedule for antitumor activity on Yoshida sarcomas in rats was found to be infusion of 5‐FU at 5 mg/kg over 24 h for 6 consecutive days, which gave a plasma 5‐FU level of 176 ng/ml. Continuous infusion of 5‐FU to give a plasma level of 300 ng/ml for 6 consecutive days from day 5 after implantation of tumor cells, when the tumors weighed about 1.0 g, resulted in complete regression of the tumors in all rats.
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