title: Gastric microbleeding following single and repeated dosing with naproxen.
abstract: BACKGROUND
  Adaptation to gastric damage from nonsteroidal anti-inflammatory drugs (NSAID) has been observed during ongoing dosage in rats and humans. However, this does not always occur, and our previous data suggest that NSAID half-life may be a determining factor.
  
  
  OBJECTIVE
  To investigate whether adaptation occurs during 1 week of naproxen administration in humans.
  
  
  METHODS
  Thirteen healthy volunteers were studied at baseline, and after one or seven daily doses of naproxen 750 mg. Gastric microbleeding was measured 4 h after naproxen in gastric washings collected during a 30-min period. Serum thromboxane B concentrations were also assayed, as a marker of cyclo-oxygenase inhibition.
  
  
  RESULTS
  Mean blood loss after placebo was 0.60 microL/10 min (95% CI: 0.21-0.98). This rose to 2.15 (0.73-3.57) and 1.75 (0.74-2.76) microL/10 min after one and seven daily doses of naproxen, respectively (P < 0.05 vs. baseline; day 1 vs. 7 not significant). Thromboxane B concentrations were < 10% of control at both day 1 and 7 of dosing.
  
  
  CONCLUSIONS
  In accord with our findings in rats, adaptation to this moderately long acting NSAID in humans was not apparent. We conclude that any adaptation to naproxen is unlikely to be clinically important.
authors.affiliation: University of Melbourne Department of Medicine, Western Hospital, Footscray, Victoria, Australia.
authors.forename: M E
authors.initials: ME
authors.lastname: McAlindon
authors.forename: G A
authors.initials: GA
authors.lastname: Cook
authors.forename: S L
authors.initials: SL
authors.lastname: Elliott
authors.forename: C J
authors.initials: CJ
authors.lastname: Hawkey
authors.forename: N D
authors.initials: ND
authors.lastname: Yeomans
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D005260:Female; D005751:Gastric Lavage; D006471:Gastrointestinal Hemorrhage / Q000097:blood / Q000139:chemically induced*; D006801:Humans; D008297:Male; D009288:Naproxen / Q000009:adverse effects*; D013272:Stomach Diseases / Q000097:blood / Q000139:chemically induced*; D013931:Thromboxanes / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013931:Thromboxanes; D009288:Naproxen