Differences in antiaggregating activity of dipyrone in whole blood and in platelet-rich plasma

Platelet aggregation in whole blood and platelet-rich plasma (PRP) and thromboxane A₂ (TxA₂) production in serum were investigated in ten healthy subjects before and at various intervals (1, 3, 8, and 24 hours) after single and repeated (7 days) oral administrations of dipyrone in different dosages (50, 100, 250, 500, and 1,000 mg). A dose-dependent inhibition of platelet aggregation (r = .90; P <0.001) induced by 1.5 mg/L collagen in PRP and of TxA₂ production (r = .88; P <0.001) was found three hours after drug administration and progressively decreased after eight and 24 hours. Interestingly, a statistically significant (P <0.001) inhibitory effect of dipyrone on platelet aggregation was also observed in whole blood, but it was consistently lower than that in PRP, suggesting an important interference of white blood cells with platelet functions and with the antiplatelet drug effects. The seven-day treatment, probably increasing or accelerating liver drug metabolization, induced a decrease in the duration of action on platelet aggregation and TxA₂ production compared with single administration.