Effect of erythrocyte binding on elimination of harmol by the isolated perfused rat liver

Abstract

The effect on the hepatic elimination rate of drug bound to erythrocytes and to albumin was compared with harmol, a relatively hydrophilic drug of high hepatic intrinsic clearance, in the single-pass isolated perfused rat liver preparation (n = 12). The steady-state hepatic extraction ratio (E) of harmol (50 μM) was measured during three consecutive 35-min periods with three different perfusates: Krebs-Henseleit butter, buffer containing bovine serum albumin (2%), and buffer containing washed human erythrocytes (10%) perfused at 5 mL/min/g liver in randomized order. The mean unbound fraction (f(u)) of harmol in the latter two perfusates was 0.55 ± 0.07 and 0.62 ± 0.08, respectively, and the ..