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Drug Res (Stuttg) 2013; 63(12): 620-624
DOI: 10.1055/s-0033-1349837
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Comparison of the Exposure of Glycyrrhizin and its Metabolites and the Pseudoaldosteronism after Intravenous Administration of Alpha- and Beta-glycyrrhizin in Rat

R. Xu
1   Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
,
Q. Xiao
1   Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
,
Y. Cao
1   Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
,
J. Yang
1   Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China
› Author Affiliations
Further Information

Publication History

received 06 April 2013

accepted 18 June 2013

Publication Date:
17 July 2013 (online)

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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.

Key words

glycyrrhetinic acid - 3-monoglucuronyl-­glycyrrhetinic acid - isomer - systemic exposure - pseudoaldosteronism
 

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