新制癌剤5-Fluoro-1,3-bis(tetrahydro-2-furanyl)-2,4-pyrimidinedione(FD-1)の生体内運命(第1報)経口投与による吸収, 分布, 代謝および排泄

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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.
社団法人日本薬学会の論文
1978-04-25