Effects of fenflumizole on aggregation ex vivo of human platelets and formation of thromboxane B2 and 6-keto-prostaglandin-F1 alpha.
Fenflumizole (2-(2,4-difluorophenyl)-4,5-bis(4-methoxyphenyl)imidazole), a new non-steroidal anti-inflammatory drug, was given to healthy subjects in single oral doses of 0.1, 1 and 2 mg/kg. The effect of the drug was followed for up to 8 h by repeated tests of arachidonic acid-induced platelet aggregation and was related to its concomitant plasma concentration. Fenflumizole reversibly inhibited platelet aggregation and the degree of inhibition was found to be linearly correlated with the log plasma concentration. There was depression of the formation of thromboxane B2 and 6-keto-prostaglandin F1 alpha (the stable metabolites of thromboxane A2 and prostacyclin) in clotted whole blood measured by radioimmunoassay after fenflumizole 1 mg/kg. This effect was directly related to the concentration of the drug in plasma, the maximum effect being reached at fenflumizole concentrations greater than 200 ng/ml. EC50-values for inhibition of the formation of thromboxane B2 and 6-keto-prostaglandin F1 alpha were approximately 20 and 40 ng/ml, respectively. The results suggest that orally administered fenflumizole is a potent inhibitor of platelet aggregation and prostanoid formation.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013931:Thromboxanes / Q000096:biosynthesis*
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D007093:Imidazoles; D013931:Thromboxanes; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C038996:fenflumizole