THE PHARMACOKINETICS OF GLYCYRRHIZIC ACID EVALUATED BY PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING†

@article{Ploeger2001THEPO,
  title={THE PHARMACOKINETICS OF GLYCYRRHIZIC ACID EVALUATED BY PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING†},
  author={B. Ploeger and T. Mensinga and A. Sips and W. Seinen and J. Meulenbelt and J. DeJongh},
  journal={Drug Metabolism Reviews},
  year={2001},
  volume={33},
  pages={125 - 147}
}
Glycyrrhizic acid is widely applied as a sweetener in food products and chewing tobacco. In addition, it is of clinical interest for possible treatment of chronic hepatitis C. In some highly exposed subjects, side effects such as hypertension and symptoms associated with electrolyte disturbances have been reported. To analyze the relationship between the pharmacokinetics of glycyrrhizic acid in its toxicity, the kinetics of glycyrrhizic acid and its biologically active metabolite glycyrrhetic… Expand
[Novel formulations of a liver protection drug glycyrrhizin].
TLDR
The utility of glycyrrhizin formulations prepared in safe solubility agents and absorption-enhancing agents, as assessed in animal experiments are described and discussed. Expand
The absorption features of glycyrrhizic acid in the drug formulation Phosphogliv
Glycyrrhizic acid (GL), one of the active components of the Russian drug formulation Phosphogliv, is characterized by extremely low bioavailability. Absorption characteristics of GL after peroralExpand
The disposition of diammonium glycyrrhizinate and glycyrrhetinic acid in the isolated perfused rat intestine and liver.
TLDR
GZ can be absorbed unchanged from the intestine provided it has sufficient time and is protected from intestinal bacteria, opening up the possibility that the use of pharmaceutical carrier systems or similar formulation approaches may allow effective oral administration of therapeutic levels of GZ without the side effects associated with GA. Expand
Comparative pharmacokinetic behavior of glycyrrhetic acid after oral administration of glycyrrhizic acid and Gancao-Fuzi-Tang.
TLDR
The results suggest the increased effect of GA after oral administration of KF in comparison with GL and the mean residence time and area under the curve of GA in KF-administered rats were significantly different from those in GL- Administered rats. Expand
3-Monoglucuronyl-Glycyrrhretinic Acid Is a Substrate of Organic Anion Transporters Expressed in Tubular Epithelial Cells and Plays Important Roles in Licorice-Induced Pseudoaldosteronism by Inhibiting 11β-Hydroxysteroid Dehydrogenase 2
TLDR
3MGA is actively transported into tubules through OATs, resulting in the inhibition of 11β-HSD2, suggesting that 3MGA levels in plasma or urine may be useful for preventing pseudoaldosteronism when licorice or GL is prescribed to patients. Expand
Down-Regulation of a Hepatic Transporter Multidrug Resistance-Associated Protein 2 Is Involved in Alteration of Pharmacokinetics of Glycyrrhizin and Its Metabolites in a Rat Model of Chronic Liver Injury
TLDR
Evaluating the pharmacokinetics of GL and its metabolites in rats with chronic liver injury induced by a choline-deficient l-amino acid-defined (CDAA) diet suggested that 3MGA would be excreted to bile via hepatic Mrp2 and that its dysfunction would reduce3MGA clearance. Expand
Glycyrrhizin and glycyrrhetinic acid directly modulate rat cardiac performance.
TLDR
To the authors' knowledge, these data reveal, for the first time, that both glycyrrhizin and glycyrrhetinic acid directly affect cardiac performance. Expand
Identification of an Alternative Glycyrrhizin Metabolite Causing Liquorice-Induced Pseudohyperaldosteronism and the Development of ELISA System to Detect the Predictive Biomarker
TLDR
The analyzing method of these metabolites as a preventive biomarker for the onset of pseudohyperaldosteronism using an enzyme-linked immunosorbent assay (ELISA) was developed, and 4 was found as the secondary candidate causative agent. Expand
Laminaria japonica increases plasma exposure of glycyrrhetinic acid following oral administration of Liquorice extract in rats.
TLDR
Laminaria increased plasma exposures of GA following oral administration of liquorice or GL, which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine. Expand
Glycyrrhizic acid and 18β-glycyrrhetinic acid recover glucocorticoid resistance via PI3K-induced AP1, CRE and NFAT activation.
  • T. Kao, Chi-Hao Wu, G. Yen
  • Biology, Medicine
  • Phytomedicine : international journal of phytotherapy and phytopharmacology
  • 2013
TLDR
This study showed that GA and 18βGA exhibit potential anti-inflammatory and antioxidant properties and provided a possible strategy for enhancing the efficacy of glucocorticoids and may improve the prognosis of patients with serious inflammatory diseases. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 89 REFERENCES
Physiologically based pharmacokinetic modeling of glycyrrhizic acid, a compound subject to presystemic metabolism and enterohepatic cycling.
TLDR
The model demonstrates that glycyrrhizic acid and metabolites are transported efficiently from plasma to the bile, possibly by the hepatic transfer protein 3-alpha-hydroxysteroid dehydrogenase, which causes the observed delay in the terminal plasma clearance of glycyrrhetic acid. Expand
Pharmacokinetic profile of glycyrrhizin in healthy volunteers by a new high-performance liquid chromatographic method.
TLDR
An improved high-performance liquid chromatographic method was developed for the quantification of glycyrrhizin and its metabolites in human plasma and showed biexponential profiles during the 24-h period after administration of each dose. Expand
Rapid estimation of glycyrrhizin and glycyrrhetinic acid in plasma by high-speed liquid chromatography.
TLDR
A method was established by which glycyrrhizin and glycyrrhetinic acid present in plasma can be extracted with methanol and then separated and determined quantitatively within 10 min by means of high-speed liquid chromatography, and showed that G is absorbed in rat small intestine in an apparent first-order process. Expand
Analysis and pharmacokinetics of glycyrrhizic acid and glycyrrhetinic acid in humans and experimental animals
TLDR
While GZA can be eliminated unmetabolized and undergoes enterohepatic cycling, GRA is conjugated to GRA glucuronide or sulfate prior to biliary excretion, which means the major part of both GRA or GZA is eliminated by the bile. Expand
A population physiologically based pharmacokinetic/pharmacodynamic model for the inhibition of 11-beta-hydroxysteroid dehydrogenase activity by glycyrrhetic acid.
TLDR
Due to the relationship between the pharmacokinetics of glycyrrhetic acid and its inhibitory effect on 11-beta-hydroxysteroid dehydration activity, reflected by a change in the urinary cortisol-cortisone ratio, this ratio might serve as a noninvasive marker to identify individuals at risk for glycyrrhizic acid over-consumption. Expand
Glycyrrhizic acid in liquorice--evaluation of health hazard.
  • F. C. Størmer, R. Reistad, J. Alexander
  • Chemistry, Medicine
  • Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 1993
TLDR
It is not possible, on the basis of existing data, to determine precisely the minimum level of glycyrrhizic acid required to produce the described symptoms, but an uneven consumption pattern suggests that a considerable number of individuals who consume large amounts of liquorice sweets are exposed to the risk of developing adverse effects. Expand
Intestinal bacterial hydrolysis is indispensable to absorption of 18β‐glycyrrhetic acid after oral administration of glycyrrhizin in rats
TLDR
These findings indicate that orally administered glycyrrhizin is poorly absorbed from the gut, but is hydrolysed to 18β‐glycyrrhetic acid by intestinal bacteria such as E. sp. Expand
Pharmacokinetics of glycyrrhetic acid, a major metabolite of glycyrrhizin, in rats.
TLDR
The pharmacokinetics of GLA in the rat is dose-dependent owing to a saturable elimination rate and is accounted for by the intestinal reabsorption ofGLA produced from GLZ and GLA-conjugates during the enterohepatic recycling of both. Expand
Kinetics and dynamics of orally administered 18 beta-glycyrrhetinic acid in humans.
TLDR
Based on the single dose kinetics, the kinetic/dynamic analysis of the data revealed that after multiple doses of 1. Expand
The metabolism of carbenoxolone in the rat.
TLDR
The figures suggest that hydrolysis of [14C] carbenoxolone into [ 14C]succinate plus 18β-glycyrrhetic acid occurs in the gastrointestinal tract before absorption, the latter being further metabolized to 14CO2. Expand
...
1
2
3
4
5
...