Studies on absorption, distribution and excretion of 14C labeled (+-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2,4-difluorophenyl)-1,4- dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid p-toluene-sulfonate hydrate (14C-T-3262) in rats and mice

Abstract

Absorption, distribution and excretion of T-3262 were studied in rats and mice after oral administration of 14C-T-3262. The obtained results are summarized as follows. 1. 14C-T-3262 was absorbed from the upper small intestine such as duodenum in rats. 2. Serum levels of radioactivity in rats reached the highest concentration at 1 hour after an oral administration, then gradually diminished. 3. Urinary excretion was 35% and 42% of the dosed radioactivity in rats and mice, respectively, and fecal excretion was about 65% and 56% of the dosed radioactivity in rats and mice, respectively. 4. Biliary excretion in rats was about 27% of the dosed radioactivity after an oral administration of 14C-T-3262, and a half amount of excreted radioactivity was reabsorbed from the intestine. 5. Radioactivity was distributed the most into the kidney and the liver among all organs other the stomach and the intestine. Radioactivity was widely distributed into other organs such as spleen, adrenal, pancreas, lung, heart and thymus. But the distribution of radioactivity into the brain was little. 6. The distribution of 14C-T-3262 was also studied with whole body autoradiography in normal male mice and pregnant mice. The radioactivity was distributed widely to whole tissues except brain, spinal cord and eye ball. In pregnant mice, radioactivity levels in the fetuses were the same as the blood level of the mother mice. 7. The binding rate of 14C-T-3262 to rats and mice serum proteins was 63-66%. 8. Urinary and fecal excretion patterns of radioactivity in mice after multiple oral administration of 14C-T-3262 for 10 days were similar to those after a single administration. This result suggests that T-3262 did not accumulate in body. 9. After oral administration of 14C-T-3262 to nursing rats, the secreted radioactivity level in the milk was higher than the blood level.