Time course inhibition of gastric and platelet COX activity by acetylsalicylic acid in humans

Aspirin causes peptic ulcers predominately by reducing gastric mucosal cycl ooxygenase (COX) activity and prostaglandin synthesis. Because aspirin circ ulates for only a few hours, we hypothesized that aspirin's inhibitory effe ct on gastric COX activity must be prolonged. We performed a placebo-contro lled experiment in healthy humans to determine the duration of inhibition o f aspirin on gastric mucosal COX activity (PGE(2) and PGF(2 alpha) synthesi s rates). Recovery of gastric COX activity after stopping aspirin was slow and linear. Seventy-two hours after 325-mg aspirin, gastric COX activity wa s still reduced by 57% (P< 0.001). Duration of inhibition of gastric COX ac tivity was estimated to be 7-8 days after 325-mg aspirin and 5 days after 8 1-mg aspirin. Recovery of gastric prostaglandin synthesis after 325-mg but not after 81-mg aspirin occurred at slower rates in subjects with Helicobac ter pylori-associated gastritis than in those with normal histology. In con clusion, aspirin inhibits gastric COX activity for much longer than predict ed from its pharmacokinetic profile, explaining why aspirin at widely space d intervals is ulcerogenic.