title: Factors affecting the plasma protein binding of verapamil and norverapamil in man.
abstract: The in vitro and vivo binding of the antiarrhythmic agent verapamil and its active metabolite norverapamil to human plasma proteins was determined under different conditions at 37 degrees C by equilibrium dialysis. The binding of verapamil was considerable (free fraction of about 0.10) and was independent of plasma concentration over the range of 50 ng/ml to 1500 ng/ml. Norverapamil was also extensively bound to plasma proteins. Verapamil binding was reduced significantly upon plasma dilution and upon addition of three of its major metabolites (norverapamil and metabolites A and B). Therapeutic concentrations of several drugs including disopyramide (12 micrograms/ml), diazepam (2 micrograms/ml), lidocaine (4 micrograms/ml), propranolol (150 ng/ml), and salicylate (250 microgram/ml) also significantly increased the free fraction of verapamil. The results of in vivo protein binding studies using plasma samples collected during a steady-state dosing interval from a patient receiving 80 mg of verapamil orally every 6 hr were similar to those obtained from vitro binding studies.
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D011485:Protein Binding; D013997:Time Factors; D014700:Verapamil / Q000031:analogs & derivatives* / Q000097:blood*
chemical_list: D001798:Blood Proteins; C016904:norverapamil; D014700:Verapamil