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Journal of Clinical Endocrinology & Metabolism, Vol 78, 581-585, Copyright © 1994 by Endocrine Society

ARTICLES

Kinetics and dynamics of orally administered 18 beta-glycyrrhetinic acid in humans

S Krahenbuhl, F Hasler, BM Frey, FJ Frey, R Brenneisen and R Krapf
Division of Clinical Pharmacology and Toxicology, University Hospital of Zurich, Switzerland.

18 beta-Glycyrrhetinic acid (GRA) represents a major metabolite of glycyrrhizic acid (glycyrrhizin), an important constituent of licorice and licorice root, and is a potent inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta OHSD). Different oral doses of GRA (500, 1000, or 1500 mg) were administered to healthy volunteers in order to study its kinetics and dynamics. In agreement with the lipophilic nature of GRA, with a biphasic decay of the plasma concentration-time curve at doses greater than 500 mg. The mean (+/-SEM) half-life of the second elimination phase was 11.5 +/- 1.2 h after 1000 mg GRA and 38.7 +/- 10.5 h after 1500 mg GRA (P < 0.05). The peak plasma concentration and the area under the plasma concentration-time curve (AUC) increased with increasing GRA doses. Urinary elimination of GRA and GRA glucuronides over 24 h was less than 1% of the dose administered. The dynamics of GRA were assessed by measuring the activity of the 11 beta OHSD in vivo, as reflected by the cortisol and cortisone concentrations in plasma. With increasing doses of GRA, the cortisone concentration declined, and the cortisol/cortisone ratio increased. Both peak plasma concentration and AUCs of GRA correlated with changes in the AUC values of cortisone. Based on the single dose kinetics, the kinetic/dynamic analysis of the data revealed that after multiple doses of 1.5. g GRA/day, the 11 beta OHSD might be constantly inhibited, whereas at daily doses of 500 mg or less, such an inhibition might occur only transiently.


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