Plasma levels of salicylate and aspirin in healthy volunteers: relevance to drug interaction on platelet function.

Salicylate can prevent the inhibitory effect of aspirin on platelet cyclooxygenase activity. We investigated whether salicylate and aspirin interact in platelets in humans at doses and plasma levels of clinical relevance. In our first experiment in healthy volunteers, the lowest dose of intravenously administered aspirin that suppressed arachidonate-induced platelet aggregation and serum immunoreactive thromboxane B2 generation was 40 mg. In our second experiment, volunteers given oral doses of sodium salicylate (250 or 1000 mg) had peak plasma salicylate levels averaging 20 and 76 micrograms/ml, respectively. Neither platelet aggregation or thromboxane B2 formation was modified by either salicylate treatment. Forty minutes later, all six volunteers received 40 mg of aspirin intravenously. Aspirin levels were not affected by previous salicylate ingestion, but inhibition by aspirin of both platelet aggregation and thromboxane B2 generation was significantly prevented by the higher salicylate dose. In our last experiment, peak plasma levels of aspirin and salicylate were measured in healthy volunteers after ingestion of either 320 mg of compressed or 800 mg of enteric-coated aspirin. Salicylate levels averaged 19 and 51 micrograms/ml, respectively, after the lower and higher doses of aspirin, whereas aspirin averaged 3 micrograms/ml after either dose. Serum thromboxane B2 generation was almost completely inhibited 1 hour after either aspirin dose.(ABSTRACT TRUNCATED AT 250 WORDS)