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 concentration range of .8 to 64 micrograms/mL. Increase in free fraction at higher plasma drug concentrations corresponded directly to the dose-dependent increase in renal drug clearance. Nonlinear parameter estimation showed that FCE 22,178 binds tightly to plasma proteins with an apparent 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.
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Department of Pharmacokinetics/Dynamics Medical Research Center, Adria Laboratories, Columbus, OH 43216-6529.
Rossi
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Narang
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D001798:Blood Proteins / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D008297:Male; D009281:Naphthalenes / Q000378:metabolism*; D011485:Protein Binding; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D001798:Blood Proteins; D007093:Imidazoles; D009281:Naphthalenes; D013930:Thromboxane-A Synthase; C066217:rolafagrel