Pharmacokinetic Modulation of Plasma 5‐Fluorouracil Concentrations to Potentiate the Antitumor Activity of Continuous Venous Infusion of 5‐Fluorouracil

Methods for pharmacokinetic modulation of the plasma 5‐fluorouracil (5‐FU) level to increase antitumor activity during continuous venous infusion (CVI) of low doses of 5‐FU were examined in Yoshida sarcoma‐bearing rats. These methods were additional infusion of 5‐FU for a short period (4 h) or oral administration of LIFT or Tegafur during long‐term CVI of 5‐FU that alone gave a plasma 5‐FU level of about 50 ng/ml. The antitumor effect on Yoshida sarcoma was markedly potentiated when an additive dose of 5‐FU combined with 3‐cyano‐2,6‐dihydroxypyridine (CNDP), a potent inhibitor of 5‐FU degradation, giving a plasma level of about 500 ng/ml, was infused for 4 h. A similar increase in the antitumor effect was observed with oral administration of a conventional dose of UFT during CVI of 5‐FU without CNDP, giving a plasma level of 30 to 60 ng/ml. These results suggest that the antitumor effect of CVI of 5‐FU can be potentiated by pharmacokinetic modulation of the 5‐FU concentration in the blood.