Activity of dipyrone on intraplatelet arachidonic acid metabolism: an in vitro study.

The effects of dipyrone on platelet cyclooxygenase and lipoxygenase were investigated in vitro by the study of 1-14C arachidonic acid (AA) conversion by high performance liquid chromatography (HPLC) on washed platelets at seven different drug concentrations (from 5 to 300 micrograms/ml). The effects of dipyrone on thromboxane (TX) B2 generation from endogenous AA were also studied in platelet-rich plasma and in washed platelets by radioimmunoassay. In the study of 1-14C AA metabolism the inhibitory concentration (IC) 50 for TXB2 was 40 micrograms/ml. However, at the lowest drug concentration (5 micrograms/ml) a slight but significant inhibition was found (25.3%, P less than 0.001) and a complete one at 300 micrograms/ml. A relationship between TXB2 inhibition and log drug concentration was found (r = 0.97, P less than 0.001). Lipoxygenase (LO) activity showed an increase of 45.9% at 20 micrograms/ml and of 251.5% at the highest concentration (r = 0.97, P less than 0.001). The inhibition of TXB2 generation from endogenous AA by washed platelets was of the same order of magnitude of the inhibition of TXB2 production from exogenous 1-14C AA. Our results indicate that dipyrone affects intraplatelet AA metabolism at very low concentrations, however its activity, on a molar ratio basis, appears to be lower than that of other non-steroidal anti-inflammatory drugs.