The effects of a 7.5-day course of orally administered salsalate (3.0 g/day), aspirin (3.9 g/day), or placebo on gastroduodenal mucosal injury, mucosal prostaglandin content, and plasma prostaglandin concentrations in healthy, asymptomatic human volunteers were examined. Mean serum salicylate concentrations after these doses of salsalate and aspirin were nearly identical (≈15 mg/dL). When the gastroduodenal mucosa was assessed endoscopically 1 hour after the final dose of medication, there was minimal mucosal injury in placebo-treated or salsalatetreated subjects and considerable injury in the stomach and duodenum of aspirin-treated subjects (P < 0.001, aspirin vs. salsalate or placebo). In both the stomach and duodenum, aspirin lowered mucosal prostaglandin F2a and E2 content by > 90% (P < 0.001), whereas salsalate produced no significant change. Aspirin also lowered plasma prostaglandin F2a concentrations by 58% ± 6%, whereas salsalate lowered them by only 11% ± 9% (P < 0.001). Thus, the nonacetylated salicylate, salsalate, produced much less gastroduodenal mucosal damage than aspirin at equivalent serum salicylate concentrations, possibly because salsalate did not inhibit mucosal prostaglandin synthesis.
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