Studies on the Fate of 5-Fluoro-1, 3-bis (tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FD-1), a New Antitumor Agent. I. Absorption, Distribution, Excretion and Metabolism of FD-1 administered orally to Rats

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Abstract
After oral administration of FD-1, the level of 5-fluoro-2,4-pyrimidinedione (5-FU) was 5-7 times higher in the plasma and normal tissues and 8-12 times higher in tumor tissue than after administration of 5-fluoro-1-(tetrahydro-2-furanyl)-2,4-pyrimidinedione (FT). 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 .mu.g/g 12 h 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. A large amount of 5-FU formed after administration of FD-1 is formed via 3-FT. .gamma.-Hydroxybutyric acid was formed in vivo and in vitro from the tetrahydrofuranyl group of FD-1.

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