A profile of the gastric ulcerogenic activity of benoxaprofen compared with other nonsteroidal anti-inflammatory drugs in rats, stressed or given alcohol, and in pigs.
The effects of single or multiple oral administration of benoxaprofen on the gastric mucosa of stressed and unstressed rats and pigs were compared with other nonsteroidal anti-inflammatory drugs. The results showed that benoxaprofen had low ulcerogenic activity when compared with other drugs of low (e.g. azapropazone, fenclofenac) or high (e.g. aspirin, diclofenac, indomethacin) ulcerogenicity. The low ulcerogenicity of benoxaprofen observed in rats also was confirmed in ten-day studies in pigs. Benoxaprofen showed relatively little interaction with physical stress (in rats exposed to cold). Likewise, no enhancement in ulcerogenicity was observed in experimentally induced disease stress states (i.e. in adjuvant arthritis rats), or following acute or chronic oral administration of alcohol, given concurrently with the drug. Little gastric mucosal damage was observed following acute or chronic parenteral (subcutaneous or intraperitoneal) administration of the sodium salt of benoxaprofen to stressed (cold, 4 degrees C) or unstressed rats. This observation combined with evidence of good absorption of the drug suggests that the relatively low ulcerogenicity of benoxaprofen may be due to its intrinsic biochemical properties. The low activity of benoxaprofen as an inhibitor of prostaglandin synthesis may be one factor contributing to this low ulcerogenic activity.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D001169:Arthritis, Experimental / Q000503:physiopathology; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D011422:Propionates / Q000009:adverse effects*; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced*; D013312:Stress, Physiological / Q000503:physiopathology*; D013552:Swine
D000893:Anti-Inflammatory Agents; D011422:Propionates; D011453:Prostaglandins; C011677:benoxaprofen; D000431:Ethanol