Comparison of the exposure of glycyrrhizin and its metabolites and the pseudoaldosteronism after intravenous administration of alpha- and beta-glycyrrhizin in rat.

Glycyrrhizin, the major bioactive component in licorice root extract, exists as 2 isomers, α and β-glycyrrhizin, and is associated with causing pseudoaldosteronism due to its principal metabolites, glycyrrhetinic acid and 3-monoglucuronyl-glycyrrhetinic acid. The aim of this study was to compare (a) the pharmacokinetics of glycyrrhizin and its metabolites in rat after the first and last intravenous doses of either α- or β-glycyrrhizin administered once a day over 6 days, (b) kidney levels of the metabolites at 24 h after the last dose and (c) the urinary cortisol:cortisone ratio (as a biomarker of pseudoaldosteronism) in total urine collected for 24 h after the last dose.After the first dose, the clearance of glycyrrhizin in rats given α-isomer was significantly higher than in those given β-isomer and the AUC0-24 h values of glycyrrhizin and the metabolites were all significantly higher in β group than in α group. After the last dose, the AUC0-24 h values of glycyrrhizin and its metabolites were again significantly higher in rats given β-isomer than those given α-isomer and were all higher than the corresponding values after the first dose. Moreover, only kidney levels of glycyrrhetinic acid were detected in β group. The urinary cortisol:cortisone ratio was higher in rats given β-isomer and the correlation coefficients of the ratios with the AUC0-24 h values of 2 metabolites were 0.81 and 0.89 respectively.The results of the present study indicate that α-glycyrrhizin is a safer drug than β- glycyrrhizin probably due to a lower systemic exposure to the 2 metabolites. © Georg Thieme Verlag KG Stuttgart · New York.