Importance of local versus systemic effects of non-steroidal anti-inflammatory drugs in increasing small intestinal permeability in man

Increased small intestinal permeability caused by non-steroidal anti-inflammatory drugs (NSAIDs) is probably a prerequisite for NSAID enteropathy, a source of morbidity in patients with rheumatoid arthritis. This increased small intestinal permeability may be a summation of a local effect during dru...

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Bibliographic Details
Published in:Gut 1991-03, Vol.32 (3), p.275-277
Main Authors: Bjarnason, I, Fehilly, B, Smethurst, P, Menzies, I S, Levi, A J
Format: Article
Language:English
Subjects:
Adult
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Butanones - pharmacology
Double-Blind Method
Edetic Acid - pharmacokinetics
Female
Glucose - pharmacokinetics
Humans
Indomethacin - pharmacology
Intestinal Absorption - drug effects
Intestine, Small - drug effects
Male
Nabumetone
Random Allocation
Rhamnose - pharmacokinetics
Xylose - pharmacokinetics
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Summary:Increased small intestinal permeability caused by non-steroidal anti-inflammatory drugs (NSAIDs) is probably a prerequisite for NSAID enteropathy, a source of morbidity in patients with rheumatoid arthritis. This increased small intestinal permeability may be a summation of a local effect during drug absorption, a systemic effect after absorption, and a local effect of the drug excreted in bile, but the relative contribution made by these factors is unknown. We assessed the effect of indomethacin and nabumetone on intestinal permeability. The principal active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid, is not subject to appreciable enterohepatic recirculation. Twelve volunteers were studied before and after one week's ingestion of indomethacin (150 mg/day) and nabumetone (1 g/day) with a combined absorption/permeability test. Neither drug had a significant effect on the permeation of 3-0-methyl-D-glucose, D-xylose, and L-rhamnose. Indomethacin increased the permeation of radioactive 51chromium ethylenediaminetetra-acetic acid (51Cr EDTA) significantly from baseline (mean (SEM) 0.63 (0.09)% v 1.20 (0.14)%, p less than 0.01) but nabumetone did not (0.70 (0.10)% p greater than 0.1). These results were supported by the 51Cr EDTA/L-rhamnose urine excretion ratios, which reflect changes in intestinal permeability. They suggest that NSAIDs increase intestinal permeability during absorption or after biliary excretion and that the systemic effect is of minor importance.
ISSN:0017-5749
1468-3288
1458-3288
DOI:10.1136/gut.32.3.275