Detection of naproxen-induced intestinal permeability change may be facilitated by adding a standardized meal but not by forming marker ratios.

Abstract

We recently compared the intestinal permeability markers polysucrose (PS) 15,000, 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. Seventeen healthy volunteers ingested a solution containing PS 15,000, 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. The excretion of the paracellular permeability markers PS 15,000 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 15,000. Calculating a paracellular/transcellular ratio or correcting excretion values for urinary volume did not improve the differentiation. A standardized liquid meal may improve the capacity of permeability tests to distinguish between healthy and NSAID-damaged intestine.