Dose effects of aspirin on gastric prostaglandins and stomach mucosal injury

Objective: To determine if a dose of aspirin exists that might inhibit thromboxane-dependent platelet function without causing gastric mucosal injury, we studied the effects of a wide range of doses of aspirin (3 mg/d to 2600 mg/d) on gastric juice prostaglandins (PGE₂ and PGF(2α)), on serum thromboxane B₂, and on stomach mucosal injury as reflected by gastric juice hemoglobin and DNA concentrations. Design: A randomized, placebo-controlled study. Setting: Research laboratory at a Veterans Affairs medical center. Participants: 16 healthy volunteers (5 men and 11 women). Intervention: In the first part of the study, volunteers received placebo; aspirin, 324 mg/d; 1300 mg/d; or 2600 mg/d for 2 days. In the second part, volunteers received placebo; aspirin, 3 mg/d; 10 mg/d; 30 mg/d; or 81 mg/d for 8 days. Measurements: Gastric juice PGE₂ and PGF(2α), hemoglobin and DNA concentrations; gastric juice volume and acidity; and serum salicylate and thromboxane B₂ concentrations. Results: In the first part, significant and similar (approximately 50%) inhibition of gastric juice prostaglandin output was observed with daily aspirin doses of 324 to 2600 mg. However, a significant increase in gastric juice hemoglobin output occurred only with 2600 mg/d. In the second part, significant inhibition (approximately 50%) of gastric PGE₂ output was noted at a daily aspirin dose of 30 mg. Lower aspirin doses did not reduce PGE₂ output significantly, although these doses did significantly reduce serum thromboxane B₂ in a dose-related manner. Conclusions: Aspirin can significantly reduce serum thromboxane B₂ at doses of 3 mg/d or 10 mg/d, which are significantly below the threshold dose for significant gastric prostaglandin inhibition and acute stomach mucosal injury.