A DOSE‐RANGING STUDY OF THE ANTIPLATELET EFFECT OF ENTERIC COATED ASPIRIN IN MAN

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Abstract
Enteric coated aspirin was given to eight human volunteers in escalating doses (20, 40,60,80,100 mg daily), each dose being given over two weeks. In addition, to measure the maximum effect of aspirin, each volunteer was given two single doses of 600 mg of soluble aspirin. At the end of each dosing interval we measured platelet aggregation and thromboxane formation in response to four aggregating agents and to whole blood coagulation. The doses of aspirin required to inhibit platelet aggregation in response to various stimuli were: for collagen 60–80 mg, for adenosine diphosphate and adrenaline 60 mg, and for arachidonate 40 mg. For maximum inhibition of thromboxane formation the doses were: for collagen greater than 100 mg, for adenosine diphosphate and adrenaline 60 mg, for arachidonate 80 mg, and for whole blood coagulation 100 mg. Different aspirin doses are required to inhibit the responses to different stimuli. Furthermore, for some stimuli, inhibition of thromboxane generation may require more aspirin than is required for inhibition of aggregation. The clinical implications of these findings are uncertain since we do not know which stimuli are important in arterial thrombosis in man.