Flurbiprofen,a new potent inhibitor of platelet aggregation

Flurbiprofen [dl-2-(2-fluoro-4-biphenylyl)propionic acid] is a non-steroidal anti-inflammatory compound whose inhibitory activity on collagen-induced platelet aggregation approaches the activity seen with prostaglandin E₁ (PGE₁). However, unlike PGE₁, it does not cause an increase in platelet cAMP levels, is orally active when given to animals or man, and is without side effects at platelet anti-aggregating doses. An oral dose of 1 mg/kg in rats inhibited collagen-induced platelet aggregation for 48 hours. At this dose, the mesenteric bleeding time in rats was prolonged from 197.2±24.4 sec. to 470.4±48.4 sec. The compound prevented death in mice due to pulmonary thromboembolism following collagen injection and inhibited platelet aggregation in man following oral administration. The drug appears to function by blocking the interaction of platelets with surfaces such as collagen but does not bind to the platelet membrane. It has no effect on the uptake of glucose or serotonin. The platelet anti-aggregating effect of flurbiprofen resides in the d-isomer while the l-isomer is without platelet anti-aggregating effect and does not counteract or enhance the effect of the d-isomer. These studies suggest that flurbiprofen may be a potentially useful antithrombotic drug.