Effect of Prostaglandin on Indomethacin-Induced Increased Intestinal Permeability in Man

Abstract

Bjarnason I, Smethurst P, Clark P, Menzies I, Levi J, Peters T. Effect of prostaglandin on indomethacin-induced increased intestinal permeability in man. Scand J Gastroenterol 1989, 24(suppl 164), 97-103

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 μg, 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 uCi, 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.

Key Words:

• Absorption
• intestinal inflammation
• non-steroidal anti-inflammatory drugs