Localization of 14C-nizatidine in the gastric wall of rats.

Nizatidine (N-[2-[[[2- [(dimethylamino)methyl]- 4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine , CAS 76963-41-2) has a selective and competitive antagonism against histamine H2-receptors. The localization of 14C-nizatidine to the parietal cells of gastric mucosa which is the effective site of nizatidine, was studied. After oral administration of 14C-nizatidine to rats, the radioactivity was rapidly distributed at higher levels in the gastric mucosa than in the plasma. The mucosal level of nizatidine at 6 h after administration was still 63.3 ng/g tissue, being similar to the effective plasma concentrations in dogs and man. Nizatidine was confirmed to be retained as an unchanged drug in the gastric mucosa, supporting the duration of pharmacological effects of nizatidine. The localization of the drug in gastric wall after intraduodenal administration was examined by means of microautoradiography. The radioactivity of 14C-nizatidine absorbed as the fine developed silver granules was widely localized into the parietal cells in the mucosal layer through the gastric wall at 30 min after administration. Also at 2 h after administration, when the suppression of gastric acid secretion was strongest, the silver granules were almost uniformly localized all over the gastric wall, but the localization was generally less dense than at 30 min.