BILIARY-EXCRETION OF GLYCYRRHIZIN IN RATS - KINETIC BASIS FOR MULTIPLICITY IN BILE CANALICULAR TRANSPORT OF ORGANIC-ANIONS

Purpose. To examine the presence of multiplicity for the biliary excre tion of xenobiotic conjugates, we studied the disposition of glycyrrhi zin (GR), which has glucuronide within its molecular structure and has the ability to inhibit the biliary excretion of liquiritigenin (LG) g lucuronides. Methods. GR was administered intravenously as a bolus to Sprague-Dawley (SD) rats which received an i.v. infusion of inhibitors (dibromo-sulfophthalein (DBSP) and indocyanine green (ICG)) at their transport maximum rates. Biliary excretion of GR was also examined in Eisai hyperbilirubinemic rats (EHBR), which have a hereditary defect i n the canalicular transport system of several organic anions. Results. Infusion of ICG did not affect the biliary excretion of GR, whereas i nfusion of DBSP reduced it significantly. The plasma concentration of GR was increased by DBSP but not by ICG. In EHBR, the biliary excretio n of GR was severely impaired, resulting in an increase in the plasma concentration of GR. Conclusions. These findings suggest (1) that the biliary excretion of GR is mediated by the system which is shared by D BSP and LG glucuronides but not by ICG and (2) that this system is her editarily defective in EHBR. Together with our previous findings, the multiplicity for the biliary excretion of organic anions is shown.