The fibrinolytic action of flufenamate and its influence on plasminogen binding to fibrin.

The effects of the synthetic fibrinolytic agent flufenamate were investigated in a purified system made up of bovine fibrin and human plasminogen. The lysis of the fibrin clots was observed after a 12-hour incubation for flufenamate concentrations ranging from 0.25 to 3 mM. Below 0.25 mM and above 3 mM, no lysis occurred, even after a longer incubation. An increase in plasminogen adsorption on the fibrin clot was also observed in the presence of flufenamate. The amount of plasminogen bound was estimated using 125I labelled Glu-plasminogen or Lys-plasminogen, in the presence of a protease inhibitor to avoid the fibrinolysis induced at lytic concentrations of flufenamate. Maximum binding was observed with both types of plasminogen at a flufenamate concentration of 2.5 mM. The binding, relatively fast at the start of incubation, slowed down progressively, but a real plateau was not reached, even after a 6-day incubation. Plasminogen binding was not saturable, suggesting a non-specific binding type. Although Lys-plasminogen binding was always greater than that of Glu-plasminogen, the effect of flufenamate was more pronounced on Glu-plasminogen binding.