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We kinetically examined tissues responsible for the conjugative metabolism (glucuronidation and sulfation) of a component in a crude drug, liquiritigenin (LG; 2,3-dihydro-7-hydroxy-2-(4- hydroxyphenyl)-(S)-4H-1-benzopyran-4-one) in rats in vivo. LG has been found to form five kinds of conjugates (4'-O-glucuronide (M1), 7-O-glucuronide (M2), 4',7-O-disulfate (M3), 4'-O-glucuronide-7-O-sulfate (M4) and 7-O-glucuronide-4'-O-sulfate (M5)). Analysis based on metabolite kinetics [K. S. Pang, J. Pharmacokin. Biopharm., 13, 633 (1985)] of the area under the plasma concentration curves (AUCplasma) and cumulative biliary excretions (Aibile) of the ligands after intravenous or hepatic portal venous administration of LG revealed that the liver has the ability to generate all the metabolites. For M1 and M2, the apparent biliary excretion clearance (CLbile,app) obtained by dividing the biliary excretion rate for the metabolite by the plasma concentration of the metabolite decreased with time, confirming that M1 and M2 were formed in the liver. To further analyze the formation rate constants for metabolites in each tissue, we measured the ligand content in several tissues after intravenous administration of LG. By correcting the content of metabolites that were taken up from the plasma, we found that the formation rates per gram of tissue were largest in the liver, except for M3. The metabolic capability of the kidney for M1 and M2 was 15% and 60%, respectively, to that of the liver whereas for M3, the metabolic ability of the kidney was 2.5-fold greater than that of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of Tissues Responsible for the Conjugative Metabolism of Liquiritigenin in Rats: An Analysis Based on Metabolite Kinetics.