A gastroprotective anti-inflammatory agent: the beta-morpholinoethyl ester of niflumic acid (morniflumate).

In several animal models orally administered morniflumate, the beta-morpholinoethyl ester of niflumic acid, proved almost equal to the parent compound in anti-inflammatory, analgesic and antipyretic activity with the advantage of complete freedom from the ulcerogenic effects of the acidic parent compound. Further, it was 5 times less active in intestinal perforation experiments and 10 times less toxic in acute toxicity experiments than niflumic acid. Bioavailability and pharmacokinetics tests after oral and intravenous administration suggest that morniflumate is absorbed as such from the gastrointestinal tract and then undergoes rapid hydrolysis in the plasma, releasing the free acidic form, the molecule responsible for the pharmacological effects. In addition to being free from ulcerogenic effects, the ester actually displayed a gastroprotective effect against the ulcerogenic effects of niflumic acid; this finding is discussed in the light of the concept of 'cytoprotection' recently reported for a series of mild gastric irritants.