Correlation between inhibitory effect on platelet aggregation and disposition of sulfinpyrazone and its metabolites in rabbits. Part I: Single dose study.

Abstract

Simultaneous evaluation of inhibition of the sodium arachidonate-induced platelet aggregation and drug disposition was studied in rabbits receiving single doses of sulfinpyrazone (SO) and its sulfide metabolite (S). The metabolism of SO was found to be interconversible with that of S. Due to the parallelism of disposition profiles, the observed concentration-related inhibition not only strongly correlated with the much more potent sulfide, but also correlated with the p-OH-sulfide (OH-S) or with a summation of two substances. Exaggeration of inhibition at 24-30 h and rebound effect at 48 h were found after the substances were administered. There may exist a circadian rhythm of platelet aggregation.