Comparative Effects Of Ibuprofen (Motrin) On Prostacyclin And Thromboxane Production

Abstract

Ibuprofen (Ibu) has potential as an anti-thrombotic agent with ability to inhibit platelet thromboxane A2 (TXA2) synthesis and to protect the ischemic myocardium. We have evaluated the effect of Ibu on prostacyclin (PGI2) production by primary cultures of human umbilical vein endothelium and TXA2 production by washed human platelets. Radioimmunoassays for 6-keto-PGF1α and TXB2, the stable end-products of PGI2 and TXA2 were employed. Bovine thrombin 0.33 U/ml was used as the stimulus for prostaglandin synthesis. Endothelial and platelet func ion was assessed using platelet adherence with 51cr-platelets to cell monolayers and platelet aggregometry. Both platelets and endothelium exhibited a similar sensitivity to Ibu. Complete inhibition of PGI2 and IXA2 production was seen after 30 min incubation with 100 #x03BC;M Ibu, 85% inhibition with 25 μM Ibu and 50% inhibition with 5 μM Ibu. In contrast to aspirin the effect of Ibu was rapidly reversible and PG synthesis in platelets returned within 5 min after removal of Ibu. In the presence of Ibu, the irreversible effect of aspirin upon TXA2 production was inhibited. When PGI2 and TXA2 production was completely inhibited by 100 μM Ibu, thrombin-induced platelet adherence increased from a baseline value of 3% to 27%. After a single oral dose of 400 mg, Ibu produces serum concentrations up to 135 #x03BC;M. If comparable mechanisms operate in vivo, Ibu has the potential to cause significant inhibition of both PGI2 and TXA2 production. Reversal of the effect appears to be prompt, but no significant differential effect upon TXA2 production, without a similar effect upon PGI2 production, was observed at any concentration of Ibu tested.