Biliary excretion of glycyrrhizin in rats: kinetic basis for multiplicity in bile canalicular transport of organic anions

Pharm Res. 1996 Dec;13(12):1833-7. doi: 10.1023/a:1016033124819.

Abstract

Purpose: To examine the presence of multiplicity for the biliary excretion of xenobiotic conjugates, we studied the disposition of glycyrrhizin (GR), which has glucuronide within its molecular structure and has the ability to inhibit the biliary excretion of liquiritigenin (LG) glucuronides.

Methods: GR was administered intravenously as a bolus to Sprague-Dawley (SD) rats which received an i.v. infusion of inhibitors (dibromosulfophthalein (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 in the canalicular transport system of several organic anions.

Results: Infusion of ICG did not affect the biliary excretion of GR, whereas infusion of DBSP reduced it significantly. The plasma concentration of GR was increased by DBSP but not by ICG. In EHBR, the biliary excretion 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 DBSP and LG glucuronides but not by ICG and (2) that this system is hereditarily defective in EHBR. Together with our previous findings, the multiplicity for the biliary excretion of organic anions is shown.

MeSH terms

  • Animals
  • Bile / chemistry*
  • Bile / drug effects
  • Bile Canaliculi / drug effects
  • Bile Canaliculi / metabolism
  • Biological Transport / drug effects
  • Glycyrrhetinic Acid / analogs & derivatives*
  • Glycyrrhetinic Acid / blood
  • Glycyrrhetinic Acid / pharmacokinetics
  • Glycyrrhizic Acid
  • Hyperbilirubinemia, Hereditary / metabolism
  • Indocyanine Green / pharmacology
  • Ions
  • Male
  • Rats
  • Rats, Mutant Strains
  • Rats, Sprague-Dawley
  • Sulfobromophthalein / analogs & derivatives
  • Sulfobromophthalein / pharmacology

Substances

  • Ions
  • Sulfobromophthalein
  • dibromosulphthalein
  • Glycyrrhizic Acid
  • Indocyanine Green
  • Glycyrrhetinic Acid