[The mechanism of anti-vascular permeability of 2-(2-fluoro-4-biphenylyl) propionic acid(Flurbiprofen) (author's transl)]

Abstract

Effect of 2-(2-fluoro-4-biphenylyl) propionic acid(Flurbiprofen, FP-70) on increased vascular permeability was studied using the potentiation of bradykinin-induced vascular permeability by prostaglandin in the guinea pig skin, as the test system. Prostaglandin E1 or E2 (1 microgram/site) alone did not show increased vascular permeability but did enhance the effect of various concentrations of bradykinin when concomitantly applied, whereas prostaglandin F2 alpha did not potentiate the effect of bradykinin on vascular permeability. Arachidonic acid (100 microgram/site) had no effect on vascular permeability when injected alone or in combination with bradykinin. However, arachidonic acid enhanced the effect of bradykinin when given 30 min before bradykinin. FP-70 had no inhibitory effect on prostaglandin E1 potentiation of bradykinin-induced vascular permeability. On the other hand, FP-70 completely abolished the enhancement of the effect of bradykinin by arachidonic acid. These results strongly suggest that anti-vascular permeability action of FP-70 may be due to inhibition of prostaglandin synthetase. Indomethacin and acetylsalicylic acid also exhibit similar effects. However, the inhibitory effect of FP-70 was 12.5 and 166.7 times as potent as indomethacin and acetylsalicylic acid, respectively.