EFFECT OF CO-ADMINISTRATION OF URACIL OR CYTOSINE ON THE ANTI-TUMOR ACTIVITY OF CLINICAL DOSES OF 1-(2-TETRAHYDROFURYL)-5-FLUOROURACIL AND LEVEL OF 5-FLUOROURACIL IN RODENTS

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 70  (2) , 209-214
Abstract
Concentration of 5-fluorouracil (5-FU) in the tumor, blood and various organs of ascites hepatoma AH130-bearing rats after administration of clinical doses of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) and uracil was examined. The concentration of 5-FU in blood was less than 0.02 .mu.g/ml with all combinations of FT-207 and uracil except high molar ratios of uracil to FT-207 (ratio, 5 and 10). On oral administration of FT-207 plus uracil in various combinations, the highest T/B (ratio of concentration of 5-FU in the tumor to that in blood) value was obtained at a ratio of uracil to h-207 of 4. With this combination, 5-FU concentration in the tumor, muscle and spleen was higher than that after administration of FT-207 alone (5 mg/kg). At clinical doses the optimum molar ratio of uracil to FT-207 is probably 4. Coadministration of cytosine enhanced the antitumor activity of FT-207 on sarcoma-180 in mice. However, cytosine enhanced the antitumor activity of FT-207 less than uracil and its coadministration resulted in a lower concentration of 5-FU in the tumor than coadministration of uracil.