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


METHODS
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.


RESULTS
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.


CONCLUSIONS
A standardized liquid meal may improve the capacity of permeability tests to distinguish between healthy and NSAID-damaged intestine.
Oman
H
H
Dept. of Clinical Immunology, Karolinska Hospital, Stockholm, Sweden.
Henriksson
A E
AE
Johansson
S G
SG
Blomquist
L
L
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D015415:Biomarkers; D004032:Diet; D004347:Drug Interactions; D004492:Edetic Acid / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics* / Q000652:urine; D008875:Middle Aged; D009288:Naproxen / Q000008:administration & dosage*; D010539:Permeability; D012016:Reference Values
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D008353:Mannitol; D009288:Naproxen; D004492:Edetic Acid