Gastric microbleeding following single and repeated dosing with naproxen

Area of Science:

• Gastroenterology
• Pharmacology
• Clinical Medicine

Background:

• Gastric adaptation to nonsteroidal anti-inflammatory drugs (NSAID) varies in humans and rats.
• NSAID half-life may influence the occurrence of gastric adaptation.
• Previous studies suggest inconsistent adaptation to NSAID-induced gastric damage.

Purpose of the Study:

• To determine if gastric adaptation occurs during one week of daily naproxen administration in healthy human volunteers.
• To investigate the relationship between naproxen dosage and gastric microbleeding.
• To assess cyclo-oxygenase inhibition as a marker during naproxen treatment.

Main Methods:

• Thirteen healthy volunteers received daily naproxen (750 mg) for one week.
• Gastric microbleeding was quantified in gastric washings.
• Serum thromboxane B2 concentrations were measured as an indicator of cyclo-oxygenase inhibition.

Main Results:

• Naproxen significantly increased gastric microbleeding compared to placebo after one and seven days of dosing (P < 0.05).
• No significant difference in microbleeding was observed between day 1 and day 7 of naproxen administration.
• Serum thromboxane B2 levels remained below 10% of baseline, indicating consistent cyclo-oxygenase inhibition.

Conclusions:

• Adaptation to gastric damage from naproxen was not observed in humans over a one-week period.
• The findings in humans align with previous observations in rats regarding NSAID adaptation.
• Clinically significant adaptation to naproxen is unlikely, suggesting limited protective effects against gastric damage during this period.