- 著者
- 藤井 節郎 中村 芳正 武田 節夫 森田 健一 佐藤 俊幸 丸中 照義 川口 安郎 采見 憲男
- 出版者
- The Japanese Cancer Association
- 雑誌
- GANN Japanese Journal of Cancer Research (ISSN:0016450X)
- 巻号頁・発行日
- vol.71, no.1, pp.30-44, 1980-02-29 (Released:2008-10-23)
- 参考文献数
- 14
The metabolism, antitumor activity, and acute toxicity of 5-fluoro-1, 3-bis-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FD-1) were investigated in animals, compared with 5-fluoro-1-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FT). It was found that after oral administration of FD-1, the level of 5-fluorouracil (5-FU) was maintained higher and longer than after administration of FT, and that a large amount of 5-FU was released from FD-1 by liver microsomal drugmetabolizing enzymes or spontaneous hydrolysis via 5-fluoro-3-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (3-FT) and FT. FD-1 had a significant activity against the solid form of Ehrlich carcinoma, sarcoma-180, hepatoma AH130, Yoshida sarcoma, Walker carcinosarcoma-256, and leukemia L1210 and P388, but not the ascitic forms, and it produced greater inhibition of tumor growth than FT. The acute toxicity of FD-1 was less than that of FT.
- 著者
- 川口 安郎 中村 芳正 佐藤 俊幸 武田 節夫 丸中 照義 藤井 節郎
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.98, no.4, pp.525-536, 1978-04-25 (Released:2008-05-30)
- 参考文献数
- 14
- 被引用文献数
- 5 8
After oral administration of 5-fluoro-1, 3-bis (tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FD-1), the level of 5-fluoro-2, 4-pyrimidinedione (5-FU) was 5 to 7 times higher in the plasma and normal tissues and 8 to 12 times in tumor tissue than after administration of 5-fluoro-1-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FT). Moreover, these levels were maintained longer than after administration of FT. In tumor tissue, the concentration of 5-FU was still as high as 1.42 μg/g 12 hr after administration of FD-1. FD-1 was degraded to 5-fluoro-3-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (3-FT) by liver microsomal drug-metabolizing enzymes in vitro and to FT spontaneously. Subsequently, FT was converted enzymically to the active substance, 5-FU, and 3-FT changed to 5-FU spontaneously. Conversion of FD-1 to 5-FU via 3-FT was greater than via FT. It is concluded that a large amount of 5-FU formed after administration of FD-1 is formed via 3-FT. γ-Hydroxybutyric acid was found to be formed in vivo and in vitro from the tetrahydrofuranyl group of FD-1.
- 著者
- 川口 安郎 中村 芳正 佐藤 俊幸 武田 節夫 丸中 照義 藤井 節郎
- 出版者
- 公益社団法人日本薬学会
- 雑誌
- 藥學雜誌 (ISSN:00316903)
- 巻号頁・発行日
- vol.98, no.4, pp.525-536, 1978
- 被引用文献数
- 8
After oral administration of 5-fluoro-1, 3-bis (tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FD-1), the level of 5-fluoro-2, 4-pyrimidinedione (5-FU) was 5 to 7 times higher in the plasma and normal tissues and 8 to 12 times in tumor tissue than after administration of 5-fluoro-1-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FT). Moreover, these levels were maintained longer than after administration of FT. In tumor tissue, the concentration of 5-FU was still as high as 1.42 μg/g 12 hr after administration of FD-1. FD-1 was degraded to 5-fluoro-3-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (3-FT) by liver microsomal drug-metabolizing enzymes in vitro and to FT spontaneously. Subsequently, FT was converted enzymically to the active substance, 5-FU, and 3-FT changed to 5-FU spontaneously. Conversion of FD-1 to 5-FU via 3-FT was greater than via FT. It is concluded that a large amount of 5-FU formed after administration of FD-1 is formed via 3-FT. γ-Hydroxybutyric acid was found to be formed in vivo and in vitro from the tetrahydrofuranyl group of FD-1.