ASSESSMENT OF INTESTINAL PERMEABILITY CHANGES INDUCED BY NONSTEROIDAL ANTIINFLAMMATORY DRUGS IN THE RAT

Intestinal permeability was investigated as an alternative to intestinal ulceration for measuring nonsteroidal anti-inflammatory drug (NSAID) gut damage in the rat and developed as a method for routine measurement. NSAID dose-response curves produced using the two indices of damage showed that intestinal permeability is as sensitive and reproducible 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 permeability. Measurement of [Cr-51]-EDTA permeation was found to be the most sensitive and reproducible method. Dose-response curves produced by measuring [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+)-ibuprofen. These studies show that intestinal permeability measurement is a useful alternative to other methods of assessing NSAID adverse effect and is easily and rapidly performed.