NSAID-INDUCED MUCOSAL INJURY - ANALYSIS OF GASTRIC TOXICITY OF NEW-GENERATION NSAIDS - ULCEROGENICITY COMPARED WITH ULCER HEALING

Introduction: Some non-steroidal anti-inflammatory drugs (NSAIDs) dela y healing of experimental gastric ulcers. The two experimental NSAIDs tebufelone and nitrofenac exert relatively low ulcerogenicity in vario us animal models compared with conventional NSAIDs. In addition, it ha s been reported that nitrofenac accelerates experimental acute ulcer h ealing. However, the effects of these new NSAIDs in a reliable chronic ulcer model has not been fully established. Methods: Ulcerogenicity o f tebufelone was compared with vehicle and indomethacin in arthritic f emale Lewis rats in a single dose and a 5-day dosage study. Interferen ce with ulcer healing of tebufelone and nitrofenac was compared with v ehicle, indomethacin, diclofenac, omeprazole, and indomethacin plus om eprazole in Wistar rats with gastric cryo-ulcers. The rats were treate d for 15 days and ulcer size was sequentially quantified by video endo scopy. Prostanoid synthesis in stomach and blood were assessed on day 15. Results: Ulcerogenicity of tebufelone was markedly lower than that of indomethacin using doses with equipotent anti-inflammatory activit ies. Ulcer healing was accelerated by omeprazole in the first week, bu t significantly delayed by tebufelone and nitrofenac to a similar exte nt as indomethacin and diclofenac predominantly during the second week . All NSAIDs decreased prostanoid synthesis.Conclusion: Tebufelone and nitrofenac delayed gastric ulcer healing to a similar extent as conve ntional NSAIDs even though tebufelone appears to induce less mucosal d amage when determined in standard ulcer assays in rats. Thus there doe s not appear to be a relationship between ulcerogenicity of these NSAI Ds and their behaviour in ulcer healing.