Cholestatic effects of cis-chlorprothixene on the perfused rat liver.

The cis-isomer of chlorprothixene (CPX) inhibited the excretory function of the isolated perfused rat liver. It decreased the biliary clearance and transport maximum of sulfobromophthalein (BSP). Calculation of the BSP 'clearance constants' suggested that the primary effect of the drug was on excretion and not uptake. The ability of the drug to inhibit the excretion of indocyanine green suggested that the effects of CPX were not the result of inhibition of hepatic conjugative enzymes. Measurement of 14C-erythritol clearance indicated that the deleterious effects of CPX on bile formation were at the canalicular level and that they were mainly on the bile acid-independent fraction of bile. The data indicated that the adverse effects of CPX were at the excretory level of the hepatocyte.