title: Concentration-dependent protein binding of a novel oral thromboxane synthase inhibitor--FCE 22,178.
abstract: 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.
authors.affiliation: Department of Pharmacokinetics/Dynamics Medical Research Center, Adria Laboratories, Columbus, OH 43216-6529.
authors.forename: R C
authors.initials: RC
authors.lastname: Li
authors.forename: D T
authors.initials: DT
authors.lastname: Rossi
authors.forename: P K
authors.initials: PK
authors.lastname: Narang
mesh_terms: 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*
chemical_list: D001798:Blood Proteins; D007093:Imidazoles; D009281:Naphthalenes; D013930:Thromboxane-A Synthase; C066217:rolafagrel