Inhibition of platelet function by a controlled release acetylsalicylic acid formulation--single and chronic dosing studies

Abstract

The extent to which a controlled release acetylsalicylic acid (ASA) formulation inhibited platelet function has been evaluated in single and chronic dosing studies. In the single dose study, the platelet inhibitory effect of the controlled release formulation was compared with that of an equivalent dose of soluble ASA and an equimolar dose of sodium salicylate (SA). In the chronic dosing study, ASA dose-response curves for platelet function, including cyclooxygenase activity, were determined for various doses (20-1300 mg) of the controlled release (enteric coated pellets) ASA formulation taken by volunteers daily for one week. Platelet function was assessed by the degree of inhibition of aggregation for several aggregating agents, and the degree of inhibition of activity of platelet cyclooxygenase quantified by the estimation of malondialdehyde (MDA) production. Plasma ASA and SA concentrations were also determined in each study. The controlled release product inhibited platelet function to the same extent as an equimolar dose of soluble ASA, but did so with much lower and sometimes undetectable peak systemic plasma ASA concentrations. SA, the direct metabolite of aspirin, did not have any effect on platelet function. The ASA dose-platelet function response curves obtained from chronic dosing with the controlled release formulation appeared to be similar to those reported previously for the soluble product. The inhibition of platelet function appeared to be unrelated to plasma ASA concentrations.