Abstract
Gastric ulcerogenicity was evaluated 2, 4, 6, and 24 hr after acute oral administration of various nonsteroidal anti-inflammatory drugs (NSAIDs) to 18-hr fasted rats and the time of peak ulcerogenesis determined. Meseclazone (7-chloro-2-methyl-3,3a-dihydro-2H,9H-isoxazolo-[3,2-b][1,3]-benzoxazin-9-one) was found to be the least ulcerogenic of the NSAIDs tested. Unlike the other drugs tested ulcerogenesis was not evident until the 24-hr observation period and only at the highest dose (640.0 mg/kg). The other NSAIDs exhibited gastric damage within 2–4 hr and, in order of ascending ulcerogenicity, were: diflunisal < phenylbutazone < aspirin < 5-chlorosalicylic acid (5-CSA) < fenoprofen ≅ tolmetin ≅ ibuprofen < naproxen < indomethacin. Repeated daily (4 days) administration of the NSAIDs to rats (which were fasted 18 hr prior to the fourth daily dose) appeared to increase the ulcerogenicity of the salicylic acid derivatives but not the arylalkanoic acid derivatives when calculated on a mg/kg/day basis. Nonetheless, meseclazone was the least ulcerogenic of all drugs tested and the ranking of the other NSAIDs in ascending order of gastric damage after repeated daily dosage was: phenylbutazone = diflunisal < tolmetin < aspirin < ibuprofen < 5-CSA < fenoprofen < indomethacin = naproxen.
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