Non-steroidal anti-inflammatory drugs react with two sites on platelet cyclo-oxygenase. Evidence from "in vivo" drug interaction studies in rats.

Non-steroidal anti-inflammatory drugs inhibit platelet cyclo-oxygenase activity. This study shows that salicylate, diflunisal, sulphinpyrazone and indomethacin prevention vivo aspirin inhibitory effect on cyclo-oxygenase activity as measured by the formation of malondialdehyde and thromboxane B2, two products of platelet arachidonic acid metabolism. Salicylate also prevents the inhibitory effect of indomethacin. All these drugs therefore appear to interact with the same site on platelet cyclo-oxygenase. Since salicylate is inactive by itself on this platelet enzyme and diflunisal and sulphinpyrazone were used at ineffective doses, it is suggested that their interaction with aspirin (or indomethacin) occurs at the level of a supplementary binding site, rather than directly on the substrate active site. Interaction with this putative supplementary site is necessary but not sufficient for the efficacy of these drugs on cyclo-oxygenase inhibitors. Acetylation by aspirin of the active site appears to be a phenomenon secondary to the binding of salicylate moiety to the supplementary site.