Abstract
The cytoprotective effects of misoprostol, a synthetic analog of prostaglandin E1, were investigated in healthy human subjects using randomized and placebo-controlled studies. Misoprostol significantly inhibited established aspirin (975 mg q.i.d.)-induced gastric microbleeding at 50 micrograms q.i.d., and to some extent, but not significantly, at 25 micrograms q.i.d. Misoprostol also reduced acid and chloride secretion significantly at 50 micrograms q.i.d., but not at 25 micrograms q.i.d. When administered concurrently with aspirin 650 mg q.i.d., misoprostol 25 micrograms q.i.d. significantly inhibited aspirin-induced fecal blood loss without affecting plasma salicylate concentration. The fact that misoprostol was tested at a sub-therapeutic gastric antisecretory dose (25 micrograms) indicates that the inhibition of fecal blood loss was not due to its gastric antisecretory property. Misoprostol tended to reduce antral erosion and DNA content of gastric fluid, but increased mucus concentrations in subjects with ethanol-induced damage. However, the dose of ethanol used produced gastric damage in only six of the 10 subjects and did not provide a satisfactory baseline. Misoprostol attenuated the drop in transmucosal potential difference induced by sodium taurocholate. It is concluded that misoprostol has cytoprotective activity in man. These effects may be of great importance in the treatment of acid peptic disease of the gastrointestinal tract.
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