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Physiology-Based Pharmacokinetic Study on 18β-Glycyrrhetic Acid Mono-Glucuronide (GAMG) Prior to Glycyrrhizin in Rats
To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetini...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315563/ https://www.ncbi.nlm.nih.gov/pubmed/35889533 http://dx.doi.org/10.3390/molecules27144657 |
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author | Cao, Mengxin Zuo, Jiawei Yang, Jian-Guo Wu, Chenyao Yang, Yongan Tang, Wenjian Zhu, Lili |
author_facet | Cao, Mengxin Zuo, Jiawei Yang, Jian-Guo Wu, Chenyao Yang, Yongan Tang, Wenjian Zhu, Lili |
author_sort | Cao, Mengxin |
collection | PubMed |
description | To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellent C(max) (2377.57 ng/mL), T(max) (5 min) and AUC(0-T) (6625.54 mg/L*h), which was much higher than the C(max) (346.03 ng/mL), T(max) (2.00 h) and AUC(0-T) (459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG. |
format | Online Article Text |
id | pubmed-9315563 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93155632022-07-27 Physiology-Based Pharmacokinetic Study on 18β-Glycyrrhetic Acid Mono-Glucuronide (GAMG) Prior to Glycyrrhizin in Rats Cao, Mengxin Zuo, Jiawei Yang, Jian-Guo Wu, Chenyao Yang, Yongan Tang, Wenjian Zhu, Lili Molecules Article To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellent C(max) (2377.57 ng/mL), T(max) (5 min) and AUC(0-T) (6625.54 mg/L*h), which was much higher than the C(max) (346.03 ng/mL), T(max) (2.00 h) and AUC(0-T) (459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG. MDPI 2022-07-21 /pmc/articles/PMC9315563/ /pubmed/35889533 http://dx.doi.org/10.3390/molecules27144657 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cao, Mengxin Zuo, Jiawei Yang, Jian-Guo Wu, Chenyao Yang, Yongan Tang, Wenjian Zhu, Lili Physiology-Based Pharmacokinetic Study on 18β-Glycyrrhetic Acid Mono-Glucuronide (GAMG) Prior to Glycyrrhizin in Rats |
title | Physiology-Based Pharmacokinetic Study on 18β-Glycyrrhetic Acid Mono-Glucuronide (GAMG) Prior to Glycyrrhizin in Rats |
title_full | Physiology-Based Pharmacokinetic Study on 18β-Glycyrrhetic Acid Mono-Glucuronide (GAMG) Prior to Glycyrrhizin in Rats |
title_fullStr | Physiology-Based Pharmacokinetic Study on 18β-Glycyrrhetic Acid Mono-Glucuronide (GAMG) Prior to Glycyrrhizin in Rats |
title_full_unstemmed | Physiology-Based Pharmacokinetic Study on 18β-Glycyrrhetic Acid Mono-Glucuronide (GAMG) Prior to Glycyrrhizin in Rats |
title_short | Physiology-Based Pharmacokinetic Study on 18β-Glycyrrhetic Acid Mono-Glucuronide (GAMG) Prior to Glycyrrhizin in Rats |
title_sort | physiology-based pharmacokinetic study on 18β-glycyrrhetic acid mono-glucuronide (gamg) prior to glycyrrhizin in rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315563/ https://www.ncbi.nlm.nih.gov/pubmed/35889533 http://dx.doi.org/10.3390/molecules27144657 |
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