Effect of Chlorpromazine on Hepatic Clearance and Excretion of Bile Acids by the Isolated Perfused Rat Liver 1

Abstract

Chlorpromazine (2.5 × 10^-4 M) significantly diminished the rate of bile acid excretion when added to the perfusate of the isolated perfused rat liver during a constant infusion of sodium taurocholate (40 μmol/hr). The inhibition of bile acid excretion was associated with a significant reduction of the clearance and extraction efficiency of bile acids and with an immediate and progressive increase in the perfusate concentrations of both glutamic pyruvic and glutamic oxalacetic transaminase activities. The reduced hepatic perfusion which followed the drug administration only partly accounted for the diminished bile acid excretion, as these effects of chlorpromazine on bile acid extraction and transaminase release could not be reproduced by comparable mechanical restriction of portal perfusate flow in control livers. The present findings together with previous observations demonstrating alterations in hepatic function and ultrastructure (12, 31), suggest that the inhibition of bile acid excretion by chlorpromazine in the isolated perfused rat liver is related to a generalized effect of the drug on hepatocyte plasma membranes, resulting in impairment of the uptake and eventual excretion of bile acids.