BENAZEPRIL AND BENAZEPRILAT BINDING TO ALBUMIN AND SERUM-PROTEINS

The binding of the prodrug benazepril and its active metabolite benaze prilat to human serum albumin (HSA) and to human serum proteins was st udied in vitro by equilibrium dialysis using C-14-labelled compounds. The extent of binding to serum proteins was high for both benazepril ( 94%), from 0.43 to 21.7 mu mol/l and benazeprilat (93%), from 0.5 to 2 5.2 mu mol/l. Benazepril and benazeprilat did not compete for the same site. The binding to each other was not modified in the presence of t he other. Albumin was the main protein involved in the binding (77-93% ). The binding of benazeprilat to HSA seemed to be decreased by the fa tty acid content of HSA. The binding to HSA was characterized by two c lasses of sites (k(1) = (2.6+/-1.6)x10(4) M(-1), n(1) = 0.85+/-0.31 an d k(2) = (1.0+/-0.7)x10(3) M(-1), n(2) = 7.5+/-4.0) for benazepril, an d by one class of sites (k(1) = 8.8x10(3) M(-1), n(1) = 1.2) for benaz eprilat.