Arachidonic acid-induced platelet aggregation and prostanoid formation in whole blood in relation to plasma concentration of indomethacin.

A single oral dose of indomethacin 1 mg/kg was given to 6 male and 6 female volunteers. The formation of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in clotting whole blood was measured by radioimmunoassay, and platelet aggregation induced by arachidonic acid (AA) was measured with a plasma aggregometer. The results were related to the concomitant plasma concentration of indomethacin. The maximum plasma concentration ranged between 3.24 and 8.11 micrograms/ml and the elimination half-life between 4 and 11 h. Formation of the prostanoids was reversibly inhibited, with maximum suppression when the drug concentration in plasma exceeded 0.5-1.0 microgram/ml; the IC50 was approximately 0.1 microgram/ml. Platelet aggregation was also reversibly inhibited. The correlation between the formation of prostanoids and the different phases of the aggregatory response to exogenous AA is discussed.