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Intestinal absorption characteristics of 5-fluorouracil, ftorafur and 6-mercaptopurine in rats.

The absorption characteristics of three anticancer antimetabolites, 5-fluorouracil (5-FU), ftorafur and 6-mercaptopurine (6-MP), were investigated by in vitro and in situ absorption techniques in rats. Absorption of a nucleic acid, uracil, was also investigated. In the in situ experiment, the disappearance ratios of uracil, 5-FU and 6-MP from the lumen showed a dependency on initial concentration, although ftorafur was absorbed at a constant rate regardless of the initial concentration. At low concentrations, Michaelis-Menten type processes were involved in the disappearance of uracil, 5-FU and 6-MP as judged from reciprocal plots. No metabolite of uracil, 5-FU of ftorafur was detected in the experiments. Most of the 6-MP that was lost from the lumen appeared as its metabolite, 6-thiouric acid, in the lumen. The in vitro data supported the results of the in situ experiment. In particular, uracil and 5-FU showed the ability to permeate at low concentrations against a concentration gradient. A small serosal transfer of 6-MP and the selective appearance of 6-thiouric acid on the mucosal side were confirmed. Metabolic inhibitors, 2, 4-dinitrophenol and ouabain, strongly depressed the disappearance and transfer of uracil and 5-FU, but not ftorafur. The absorption and metabolism of 6-MP were affected by 2, 4-dinitrophenol, but not ouabain.