Multiple Binding of Bepridil in Human Blood

Abstract

Using radiolabelled bepridil, equilibrium dialysis experiments and direct ligand-binding studies were conducted to characterize the binding of bepridil to some human serum proteins, and to blood cells and platelets, respectively. Bepridil was bound to serum albumin with K= 26 ± 1.6 x 10³ mol^-1 × 1, n = 1.07 ± 0.04; to α₁-acid glycoprotein with K = 442 ± 68 × 10³ mol^-1 x 1, n = 0.90 ± 0.04; and with a lesser extent to lipoproteins and γ-globulins. Bepridil, propranolol, quinidine and erythromycin were found to share the same site on αi-acid glycoprotein. The binding of bepridil to both RBC and WBC was nonspecific with the following parameters: NK = 10.55 ± 0.10 per 5 × 10⁶ RBC/mm³ and NK = 0.34 ± 0.01 per 10³ WBC/mm³, whereas the binding to platelets was saturable with N = 10.97 ± 1.06 µmol/l per 108 ± 10³ platelets/mm³ and K = 40 ± 8 × 10³ mol^-1 × 1. The binding parameters were used to simulate the distribution of bepridil between serum proteins, blood cells and platelets over the therapeutic range and showed that serum albumin, αpacid glycoprotein and RBC were the major binding components.