Comparative studies on the gastrointestinal lesions caused by several nonsteroidal anti-inflammatory agents in rats

The gastrointestinal toxicity of a single oral administration of five nonsteroidal anti-inflammatory agents (NSAIDs) to rats was compared, by a method using 51Cr-labeled red blood cells (RBC), and by macroscopic and microscopic examination. From the profile of gastrointestinal bleeding, the NSAIDs could be divided into a group consisting of aspirin (ASA), oxaprozin (OXP) and 2-[4-(3-methyl-2-butenyl)phenyl]propionic acid (TA), which caused only a transient increase in fecal blood loss based on a gastric lesion, and another group including indomethacin (IM) and ibuprofen (IP), which produced a biphasic increase in the blood loss. The initial phase was caused not only by a gastric lesion but also an intestinal lesion, and the secondary phase originated only in the intestinal lesion. The order of potency causing blood loss was IM much greater than IP greater than ASA much greater than TA greater than OXP. The safety ratio of OXP and TA was shown to be more favorable than that of the other three drugs.