title: Comparison of the exposure of glycyrrhizin and its metabolites and the pseudoaldosteronism after intravenous administration of alpha- and beta-glycyrrhizin in rat.
abstract: 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.
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
authors.forename: R
authors.initials: R
authors.lastname: Xu
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
authors.forename: J
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D019540:Area Under Curve; D003348:Cortisone / Q000652:urine; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D019695:Glycyrrhizic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D006854:Hydrocortisone / Q000652:urine; D007668:Kidney / Q000378:metabolism; D056929:Liddle Syndrome / Q000139:chemically induced*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: C052400:glycyrrhetyl 3-monoglucuronide; D019695:Glycyrrhizic Acid; D006034:Glycyrrhetinic Acid; D003348:Cortisone; D006854:Hydrocortisone