J. Ford et al., ASSESSMENT OF INTESTINAL PERMEABILITY CHANGES INDUCED BY NONSTEROIDALANTIINFLAMMATORY DRUGS IN THE RAT, Journal of pharmacological and toxicological methods, 34(1), 1995, pp. 9-16
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.