Detection of Naproxen-Induced Intestinal Permeability Change May Be Facilitated by Adding a Standardized Meal but Not by Forming Marker Ratios

Abstract

Background: We recently compared the intestinal permeability markers polysucrose (PS) 15000, ⁵¹Cr-ethylenediaminetetraacetic acid (EDTA), and ¹⁴C-mannitol in healthy humans. We have now studied the ability of these markers to show non-steroidal anti-inflammatory drug (NSAID)-induced intestinal damage, with special regard to the possibility of improving discrimination versus healthy intestine by using a hyperosmolar test solution, adding a standardized liquid meal, calculating paracellular/transcellular marker excretion ratios, or correcting excretion values for urinary volume. Methods: Seventeen healthy volunteers ingested a solution containing PS 15000, ⁵¹Cr-EDTA, and ¹⁴C-mannitol before and after 1 week of naproxen intake, the solution being isosmolar, hyperosmolar, or isosmolar and followed by a standardized liquid meal. Fractional urinary excretion of the substances was measured over 0–4 h, 4–8 h, and 8–12 h. Results: The excretion of the paracellular permeability markers PS 15000 and ⁵¹Cr-EDTA increased after NSAID pretreatment, whereas that of the transcellular marker ¹⁴C-mannitol was unaffected. A standardized liquid meal reduced test variability for all markers and tended to improve differentiation between diseased and healthy intestine. A hyperosmolar test solution tended to improve differentiation for ⁵¹Cr-EDTA but not for PS 15000. Calculating a paracellular/transcellular ratio or correcting excretion values for urinary volume did not improve the differentiation. Conclusions: A standardized liquid meal may improve the capacity of permeability tests to distinguish between healthy and NSAID-damaged intestine.

Key Words:

• Biological markers
• ethylenediaminetetraacetic acid
• intestinal absorption
• macromolecular systems
• mannitol
• molecular weight
• non-steroidal anti-inflammatory drugs
• permeability
• polysucrose