Studies on combination therapy with 1-(tetrahydro-2-furanyl)-5-fluorouracil plus uracil I. Effect of coadministration of uracil on the antitumor activity of 1-(terahydro-2-furanyl)-5-fluorouracil and the level of 5-fluorouracil in AH 130 bearing rats.

DOI Web Site 3 Citations
  • UNEMI NORIO
    Section of Pharmacology, Research Laboratory, Taiho Pharmaceutical Co., Ltd.
  • TAKEDA SETSUO
    Section of Pharmacology, Research Laboratory, Taiho Pharmaceutical Co., Ltd.
  • TAJIMA KIYOTAKA
    Section of Pharmacology, Research Laboratory, Taiho Pharmaceutical Co., Ltd.
  • KAWAGUCHI YASURO
    Section of Biochemistry, Research Laboratory, Taiho Pharmaceutical Co., Ltd.
  • YASUDA AKIO
    Section of Biochemistry, Research Laboratory, Taiho Pharmaceutical Co., Ltd.

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Other Title
  • Studies on Combination Therapy with 1-(Tetrahydro-2-Furanyl)-5-Fluorouracil Plus Uracil-1-Effect of Coadministration of Uracil on the Antitumor Activity of 1-(Tetrahydro-2-furanyl)-5-fluorouracil and the Level of 5-Fluorouracil in AH 130 Bearing Rats
  • Studies on Combination Therapy with 1 T
  • Effect of Coadministration of Uracil on the Antitumor Activity of 1-(Terahydro-2-fureny1)-5-fluorouracil and the Level of 5-Fluorouracil in AH 130 bearing Rats

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Description

Uracil has no antitumor activity, but it markedly potentiated that of 1-(tetrahydro-2-furanyl)-5-fluorouacil (FT) on AH 130, Sarcoma 180 and L 1210. It increased the 5-duorouracil (5-FU) leves in the tumor and blood when administered orally with FT to AH 130 bearing rats.<BR>The antitumor activity and 5-FU levels in the tumor and blood increased with increase in the molar ratio of uracil to FT: the 5-FU concentration in the blood increased more gradually than that in the tumor at low ratios of uracil to FT, but the 5-FU concentration in the blood increased greatly at high ratios. Consequently, the ratio of the 5-FU concentration in the tumor to that in the blood (T/B value) could be increased markedly by choosing appropriate ratios of FT and uracil. At a dose of less than 15 mg/kg of FT, a suitable ratio of uracil to FT was 1:2-4:5. With this ratio, we observed that the concentration of 5-FU in the tumor definitely increased more than that in the blood and was more than that with FT alone. UFT consists of FT and uracil in a molar ratio of 1:4. This is a reasonable ratio, judging from experimental findings. The antitumor activity of UFT on various tumor systems was about five times that of FT alone and the same as that of 5-FU. Moreover at low doses, UFT was more effective than FT or 5-FU on Lewis lung carcinoma and B 16 melanoma.

Journal

  • CHEMOTHERAPY

    CHEMOTHERAPY 29 (2), 164-175, 1981

    Japanese Society of Chemotherapy

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