CONCENTRATION-DEPENDENT PROTEIN-BINDING OF A NOVEL ORAL THROMBOXANE SYNTHASE INHIBITOR - FCE 22,178

The protein binding of FCE 22,178 in humans was determined ex vivo by equilibrium dialysis using plasma samples obtained from a dose-ranging study in normal male volunteers. These data suggested that FCE 22,178 may exhibit concentration-dependent protein binding over an in vivo c oncentration range of .8 to 64 mug/mL. Increase in free fraction at hi gher plasma drug concentrations corresponded directly to the dose-depe ndent increase in renal drug clearance. Nonlinear parameter estimation showed that FCE 22,178 binds tightly to plasma proteins with an appar ent equilibrium association constant of 1.44 X 10(5) mol/L. Predicted change in the free fraction is consistent with the observed changes in renal clearance.