Effects of ecabet sodium (TA-2711), a new antiulcer agent, on gastrointestinal mucosal prostanoid production and morphology in rats.

Effects of ecabet sodium (TA-2711), a locally acting antiulcer agent, on prostanoid production and the morphology of the rat gastrointestinal mucosa were studied in comparison with sucralfate. Ecabet, at therapeutic doses (25 and 100 mg/kg, p.o.), dose-dependently increased the gastric mucosal level of prostaglandin E2 (PGE2): sucralfate (100 mg/kg, p.o.) showed a tendency to increase the PGE2 level. In an ex vivo study, ecabet (25 and 100 mg/kg, p.o.) dose-dependently increased the capacity of the gastric mucosa to synthesize PGE2 and PGI2 without modifying tromboxane A2 (TXA2) synthesis, and the 100 mg/kg dose persisted for up to 3 h. Ecabet (400 mg/kg, p.o.) also significantly increased PGE2 synthesis and there was a tendency to increase PGI2 synthesis by the duodenal mucosa, without affecting TXA2 synthesis. PGE2 synthesis by the colonic mucosa was not affected, even at a high dose of ecabet (1000 mg/kg, p.o.). When the rat gastric mucosa was examined by light microscopy and scanning electron microscopy, ecabet (100 and 400 mg/kg, p.o.) had caused no morphological change to the gastric mucosa, while sucralfate (100 and 400 mg/kg, p.o.) produced apical rupture of the epithelial cells and subepithelial edema. The present study indicates that ecabet locally stimulates PGE2 and PGI2 production in the gastroduodenal mucosa and this effect is not attributable to a local irritant action accompanied by superficial epithelium damage.