Abstract
A controlled double blind study was performed for 29 healthy volunteers in order to assess the damaging action on the gastroduodenal mucosa induced by an inactive form of NSAIDs (as prodrug) in comparison with diclofenac Na (D) .
Subjects received either of the following three drug combinations; (1) prodrug: loxoprofen Na, L: pro-glumetacin maleate (PGM), placebo and D: placebo, (2) prodrug (PGM) L placebo and D: placebo, (3) D, L: placebo and PGM placebo. Endoscopic findings were evaluated before and 2 weeks after drug administration. Moreover, in order to investigate the mechanism of NSAIDs gastropathy, pH of gastric juice, mucosal blood flow, levels of prostaglandin E2 (PGE2) and hexosamine (H) on biopsy specimens were simultaneously measured before and after ingestion of each medication.
Gastroduodenal damages were significantly less for both prodrug group (L and PGM) compared with the D group. The enhancement of gastric acid output, decrease in mucosal blood flow and reduction of hexosamine contents were observed in D group when eompared with both prodrug group.
These findings suggest that prodrugs have a very low frequency to produce mucsosal damages, and NSAIDs gastropathy might be associated with increase of offensive factor and breakdown of defensive mechanism.
