Metabolic Fate of a New Anti-ulcer Drug (+)-(1R, 4aS, 10aR)-1, 2, 3, 4, 4a, 9, 10, 10a-Octahydro-1, 4a-dimethyl-7-(1-methylethyl)-6-sulfo-1-phenanthrenecarboxylic Acid 6-Sodium Salt Pentahydrate (TA-2711). II. Distribution in the Rat Stomach

Abstract

The distribution of (+)-(1R, 4aS, 10aR)-1-2, 3, 4, 4a, 9, 10, 10a-octahydro-1, 4a-dimethyl-7-(1-methylethyl)-6-sulfo-1-phenanthrenecarboxylic acid 6-sodium salt pentahydrate (TA-2711) in stomach was studied after oral administration of ¹⁴C-TA-2711 (100 mg/kg) to rats. At 6 h after dosing, most of the radioactivity was found in the lower intestine, caecum and large intestine. However, the radioactivity in the stomach was higher than that in the upper and middle small intestine. The concentration of the radioactivity in the glandular stomach was about 1.5 mg eq. TA-2711/g at 30 min after administration. Thereafter, it decreased gradually to about 60 μg eq. TA-2711/g at 6 h after dosing. In the radioluminograms of 6 and 24 h after dosing, most of the radioactivity was observed on the surface of gastric mucosa. After administration to rats with gastric ulcer induced by acetic acid, higher radioactivity was observed in the ulcerated tissues of the stomach than in the nonulcerated control tissues. In the stomach damaged by ethanol, the concentrations of radioactivity in lesion parts were also higher than those in non-lesion parts. In the microautoradiograms of gastric mucosa damaged by ethanol, the developed silver grains were densely distributed in necrotic tissues.