A Comparative Study of Serum Glycyrrhetinic Acid Concentrations Following Oral Administration of 24 Types of Kampo Extracts Containing Glycyrrhiza Radix in Mice

ABSTRACT Aim To examine serum glycyrrhetinic acid (GA) concentrations following oral administration of Glycyrrhiza radix (GR) containing Kampo extracts in mice. Methods We prepared 24 types of GR‐containing Kampo extracts which were orally administered to mice at 10 times the human dose. Subsequently, serum GA concentrations were measured using high‐performance liquid chromatography. In addition, glycyrrhizin hydrolysis by cecal contents and small intestinal transport were measured to clarify differences in pharmacokinetic parameters among the Kampo extracts. Results Concerning blood GA concentrations, the prescriptions showed both bimodal and unimodal profiles, which could be attributed to differences in the constituent crude drugs. We further verified that Scutellaria radix inhibited glycyrrhizin (GL) hydrolysis mediated by intestinal flora. These findings suggest that serum GA concentrations should be established for each prescription. There was a good correlation between Cmax and AUC 0‐48 ; furthermore, a strong correlation was observed between the amounts of GR or GL administered and AUC 0‐48 . In contrast, only a weak correlation was found between the amount of GR and the Cmax of GA. Given that GA enters enterohepatic circulation, AUC 0‐48 is proportional to the administered dose. However, it is influenced by factors such as the rate of intestinal absorption, as well as rates of hydrolysis and reabsorption after biliary excretion; therefore, no simple correlation with Cmax was observed. Conclusion Our findings suggest that the total amount of GA absorbed following consumption of a GR‐containing Kampo extract can be estimated from the amount of the crude drug.