GASTRIC MICROBLEEDING FOLLOWING SINGLE AND REPEATED DOSING WITH NAPROXEN

Background: Adaptation to gastric damage from nonsteroidal anti-inflam matory drugs (NSAID) has been observed during ongoing dosage in rats a nd humans. However, this does not always occur, and our previous data suggest that NSAID half-life may be a determining factor. Aim: To inve stigate whether adaptation occurs during 1 week of naproxen administra tion in humans. Subjects: Thirteen healthy volunteers were studied at baseline, and after one or seven daily doses of naproxen 750 mg. Gastr ic microbleeding was measured 4 h after naproxen in gastric washings c ollected during a 30-min period. Serum thromboxane B concentrations we re also assayed, as a marker of cyclo-oxygenase inhibition. Results: M ean blood loss after placebo was 0.60 mu L/10 min (95% CI: 0.21-0.98). This rose to 2.15 (0.73-3.57) and 1.75 (0.74-2.76) mu L/10 min after one and seven daily doses of naproxen, respectively (P < 0.05 vs. base line; day 1 vs. 7 not significant), Thromboxane B concentrations were < 10% of control at both day 1 and 7 of dosing. Conclusion: In accord with our findings in rats, adaptation to this moderately long acting N SAID in humans was not apparent. We conclude that any adaptation to na proxen is unlikely to be clinically important.