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

C. Cerletti, M. Bonati, A. Del Maschio, F. Galletti, E. Dejana, G. Tognoni, G. de Gaetano

Research output: Contribution to journalArticle

Abstract

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 μg/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 μg/ml, respectively, after the lower and higher doses of aspirin, whereas aspirin averaged 3 μg/ml after either dose. Serum thromboxane B2 generation was almost completely inhibited 1 hour after either aspirin dose. We conclude that the inhibitory effect of aspirin (40 mg, i.v.) is prevented by a previous single dose of sodium salicylate (1000 mg) giving plasma salicylate levels similar to those obtained with 800 mg of orally administered aspirin (50 to 80 μg/ml); that pretreatment with a lower dose of sodium salicylate (250 mg) giving plasma salicylate levels similar to those obtained with 320 mg oral aspirin blunts the inhibitory effect of aspirin on platelet aggregation but not on thromboxane B2 generation; and finally, that the inhibitory effect on thromboxane B2 formation of a single dose of aspirin (320 mg, compressed, or 800 mg, enteric-coated) is not prevented by the salicylate derived from its hydrolysis in vivo.

Original languageEnglish
Pages (from-to)869-877
Number of pages9
JournalThe Journal of Laboratory and Clinical Medicine
Volume103
Issue number6
Publication statusPublished - 1984

ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

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