The Biphasic Effect of Sulfinpyrazone on Platelet Function

Experiments performed in vitro have shown that the effect of sulfinpyrazone (SUL) on platelet function is associated with inhibition of platelet prostaglandin synthesis. We have studied platelet aggregation in vivo, plasma-drug levels and platelet MDA production in rabbits after treatment with SUL. At a dose of 100mg/kg, collagen-induced platelet aggregation in vivo was inhibited by 44% at ½ hr, 20% at 4 hr and then increased to a maximum inhibition of 57% at 18hr. This latter effect was achieved when there was no detectable SUL in the plasma (<0.5ug/ml). Platelets prepared from rabbits given 100mg/kg SUL either 2 or 8 hr beforehand were washed, labelled with 51Cr and injected into normal rabbits and platelet aggregation in vivo was measured. The response to collagen of platelets exposed for 2 hr to SUL was normal, whereas the response of platelets exposed for 18 hr to SUL was inhibited by 32%. MDA production by platelets incubated for 60 min in PPP prepared from rabbits which had been treated with either 10mg/ kg 1 hr beforehand or 100mg/kg 18 hr beforehand, was measured.(The SUL levels of the former and the latter plasmas were 4.4 and <0.5ug/ml respectively.) Platelet MDA production was inhibited 15% after incubation in the 10mg/kg-l hr PPP and 32% after incubation in the 100mg/kg-18 hr PPP (p<0.0001). It is concluded that SUL has a biphasic effect on collagen-induced platelet aggregation in vivo. Both effects are associated with inhibition of MDA production but the initial effect is reversible with washing and less marked than the secondary effect which is irreversible and could be due to a metabolite still present in the plasma at 18 hr.