Superior antiplatelet action of alternate day pulsed dosing versus split dose administration of aspirin.

To explore the effect of timing on the antiplatelet action of aspirin, a constant mean amount of 40 mg aspirin/day was administered either as a split regimen of 20 mg twice daily, a single dose of 40 mg or a doubled dose of 80 mg every other day for 1 week each and compared to a current standard low dose regimen of 324 mg/day. Bleeding time, serum thromboxane, collagen-stimulated platelet aggregation and associated thromboxane formation and excretion of thromboxane and prostacyclin metabolites were measured both at peak and trough action of the drug. The inhibitory effects on platelet aggregation and associated thromboxane formation were significantly less marked with the split dose regimen, intermediate with the single dose of 40 mg aspirin/day and best with the alternate day doubled dose, but still inferior to the effects of 324 mg/day. Thromboxane excretion was suppressed by greater than 80% with all regimens. Prostacyclin metabolite excretion was similar for all 40 mg/day regimens with about 40% suppression at trough and 60% at peak drug action, respectively. Suppression was more pronounced after 324 mg/day. For best platelet inactivation at comparable sparing of prostacyclin formation, low doses of aspirin should be administered in pulsed rather than split regimens.