Relationship between gastroprotective effect of locally acting antiulcer agent ecabet sodium and its binding to gastric mucosa in rats. Comparison with sucralfate.
The present study was designed to examine the relationship between the gastroprotective efficacy of the locally acting antiulcer drug ecabet sodium (ecabet) against ethanol-induced gastric lesions and the amount of the drug bound to the mucosa in comparison with sucralfate in rats. Oral administration of ecabet (25-100 mg/kg) and sucralfate (25-400 mg/kg) dose dependently prevented the formation of ethanol-induced gastric lesions, and dose dependently increased the amount of each drug bound to the gastric mucosa. Pretreatment with the antisecretory agent cimetidine (200 mg/kg, per os) significantly reduced the gastroprotective effect of sucralfate in proportion to a decrease in its binding to the mucosa. The same pretreatment tended to reduce both gastroprotection by ecabet and its binding to the mucosa. In an in vitro study using an everted stomach sac, the binding of sucralfate to the mucosa was more markedly decreased than that of ecabet on increasing the pH. These findings indicate that ecabet and sucralfate protect the gastric mucosa against ethanol in proportion to the amount of each drug bound to the gastric mucosa and that the binding of these drugs to the mucosa is under the influence of intraluminal pH. However, the gastroprotective effect of ecabet seems to be less dependent on intraluminal acidity than that of sucralfate.
Kinoshita
M
M
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Yamasaki
K
K
Kokusenya
Y
Y
Tamaki
H
H
D045784:Abietanes; D000818:Animals; D000897:Anti-Ulcer Agents / Q000378:metabolism / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D006863:Hydrogen-Ion Concentration; D008297:Male; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D013392:Sucralfate / Q000378:metabolism / Q000494:pharmacology*
D045784:Abietanes; D000897:Anti-Ulcer Agents; D004224:Diterpenes; C061681:ecabet; D000431:Ethanol; D013392:Sucralfate; D002927:Cimetidine