ASSESSMENT OF INTESTINAL PERMEABILITY CHANGES INDUCED BY NONSTEROIDALANTIINFLAMMATORY DRUGS IN THE RAT

Intestinal permeability was investigated as an alternative to intestin al ulceration for measuring nonsteroidal anti-inflammatory drug (NSAID ) gut damage in the rat and developed as a method for routine measurem ent. NSAID dose-response curves produced using the two indices of dama ge showed that intestinal permeability is as sensitive and reproducibl e as ulceration, although changes could not be detected before visible ulceration occurred. Lactulose, [Cr-51]-EDTA and [C-14]-carboxyinulin were compared as possible in vivo markers of rat intestinal permeabil ity. Measurement of [Cr-51]-EDTA permeation was found to be the most s ensitive and reproducible method. Dose-response curves produced by mea suring [Cr-51]-EDTA permeation were used to compare the potency of the two NSAIDs piroxicam and (S+)-ibuprofen; piroxicam was found to be 10 times more potent in increasing intestinal permeability than (S+)-ibu profen. These studies show that intestinal permeability measurement is a useful alternative to other methods of assessing NSAID adverse effe ct and is easily and rapidly performed.