Abstract
This study examined whether indomethacin-induced increases in small intestinal permeability in man are prevented by concomitant administration of a prostaglandin analog (misoprostol). Twelve male volunteers were tested as baseline, following misoprostol alone (200 Μg, at −16, −12, −8.5, −4, −1.5, and +4 hr); following indomethacin alone (75 mg, at −8; 50 mg, −1 hr); and following coadministration of misoprostol and indomethacin as specified above. A 100-ml test solution containing 3-O-methyl glucose (0.2 g), D-xylose (0.5 g),l-rhamnose (1.0 g), and [51Cr]EDTA (100 ΜCi) was ingested at 8 AM, and a 5-hr collection made for marker analysis to assess active and passive carrier-mediated transport and trans- and intercellular permeation, respectively. Indomethacin increased the permeation of [51Cr]EDTA selectively, and this increase was significantly reduced by the coadministration of misoprostol. These changes were mirrored by changes in [51 Cr]EDTA-L-rhamnose urine excretion ratios, which indicates that paracellular permeability was specifically altered. This study supports the suggestion that NSAIDs alter intestinal permeability by a mechanism involving reduced prostaglandin synthesis and indicates that coadministration of misoprostol with NSAIDs may reduce the frequency and severity of NSAID-induced small intestinal inflammation.
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Bjarnason, I., Smethurst, P., Fenn, C.G. et al. Misoprostol reduces indomethacin-induced changes in human small intestinal permeability. Digest Dis Sci 34, 407–411 (1989). https://doi.org/10.1007/BF01536263
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DOI: https://doi.org/10.1007/BF01536263