Biphasic initial phase of platelet aggregation inhibition after oral aspirin

For one hour after the ingestion of 1 g aspirin the pharmacodynamics of acetylsalicylic acid with regard to the inhibition of platelet aggregation were studied in nine healthy male volunteers. Plasma salicylic acid (SA) and acetylsalicylic acid (ASA) levels were measured, and platelet aggregation was controlled by the collagen-induced aggregation. It took 12 - 24 minutes till the maximum of platelet aggregation inhibition was reached; maximal inhibition was only observed with ASA levels above 4.5 /microgram/ml and total ASA levels above 10 /microgram/ml. At that time already more than 50% of the total ASA were hydrolysed to minimally active SA. In spite of further increasing ASA levels inhibition of platelet aggregation decreased again. The different sensitivity of platelet- and vessel wall cyclooxygenase to aspirin does not explain our findings.