Effect of prostaglandin on indomethacin-induced increased intestinal permeability in man.
This study examines whether NSAID induced disruption of small intestinal integrity is preventable by concomitant prostaglandin administration, and whether prostaglandins themselves interfere with intestinal permeability and absorption. Twelve subjects underwent testing following treatment as indicated: baseline, no treatment rioprostil, 300 micrograms, at -9 and -1 h indomethacin, 75 mg and 50 mg, at -9 and -1 h respectively rioprostil plus indomethacin, regimen as above. At 0800 h (0 h) subjects drink a solution containing 51CrEDTA 100 microCi, L-rhamnose 0.5 g, D-xylose 0.5 g and 3-O-methyl-glucose 0.2 g; this is followed by a 5-h urine collection. The amount of test substance in the urine reflects non-mediated intercellular and transcellular permeability, and passive and active carrier mediated transport systems, respectively. Permeation of L-rhamnose, D-xylose and 3-O-methyl-glucose is unaffected by rioprostil and/or indomethacin. Indomethacin significantly increases intestinal permeability to 51CrEDTA; coadministration of rioprostil, however, significantly decreases this detrimental effect of indomethacin. These findings suggest that prostaglandins are essential for maintaining small intestinal integrity in man and lend further support to the suggestion that NSAIDs damage the small intestine by reducing mucosal prostaglandin synthesis.
Bjarnason
I
I
Section of Gastroenterology, MRC Clinical Research Centre, Harrow, Middlesex, UK.
Smethurst
P
P
Clark
P
P
Menzies
I
I
Levi
J
J
Peters
T
T
D019325:3-O-Methylglucose; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002860:Chromium Radioisotopes; D004492:Edetic Acid; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008757:Methylglucosides; D011458:Prostaglandins E / Q000494:pharmacology*; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D012210:Rhamnose; D016630:Rioprostil; D014994:Xylose
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D002860:Chromium Radioisotopes; D008757:Methylglucosides; D011458:Prostaglandins E; D011465:Prostaglandins, Synthetic; D019325:3-O-Methylglucose; D016630:Rioprostil; D004492:Edetic Acid; D014994:Xylose; D012210:Rhamnose; D007213:Indomethacin