Misoprostol reduces indomethacin-induced changes in human small intestinal permeability.
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 micrograms, 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 microCi) 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 [51Cr]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.
Bjarnason
I
I
Section of Gastroenterology, MRC Clinical Research Centre, Harrow, Middlesex, U.K.
Smethurst
P
P
Fenn
C G
CG
Lee
C E
CE
Menzies
I S
IS
Levi
A J
AJ
D019325:3-O-Methylglucose; D000328:Adult; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D004492:Edetic Acid / Q000378:metabolism / Q000652:urine; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008757:Methylglucosides / Q000378:metabolism / Q000652:urine; D016595:Misoprostol; D010539:Permeability; D012210:Rhamnose / Q000378:metabolism / Q000652:urine; D014994:Xylose / Q000378:metabolism / Q000652:urine
D008757:Methylglucosides; D016595:Misoprostol; D019325:3-O-Methylglucose; D004492:Edetic Acid; D014994:Xylose; D000527:Alprostadil; D012210:Rhamnose; D007213:Indomethacin