Effects of some thioxanthenes on bile formation and organic anion clearance in the perfused rat liver.

Perfusion of the isolated rat liver with cis-thiothixene (THX), cis- or trans-flupenthixol (FPX), and cis- or trans-clopenthixol (CLX) has demonstrated that each of the compounds exerted adverse effects on hepatic excretory function and that their relative order of potency was THX greater than cis- = trans-FPX greater than cis- = trans-CLX. THX caused dose-dependent reductions in bile flow and sulfobromophthalein (BSP) clearance. The 14C-erythritol clearance and bile acid excretion data suggested that the primary effects of THX (10(-5)M) were on the bile acid-independent fraction of bile. The BSP kinetic data indicated that THX mainly affected the excretion of BSP and not its uptake. Since THX also decreased the excretion of indocyanine green, inhibition of hepatic conjugative enzymes did not appear to be responsible for the observed decreases in organic anion excretion. At 2.5 X 10(-5) M, both isomers of FPX reduced bile flow and BSP excretion. It took a higher concentration (7.5 X 10(-5) M) for either isomer of CLX to effect similar reductions.