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Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism

CONTEXT: Both nobiletin (NBL) and glycyrrhizin (GL) have anti-inflammatory and antitumor properties. These agents may be co-administered in the clinic. However, the drug–drug interaction between them is not clear. OBJECTIVE: The drug–drug interaction between GL and NBL was investigated, to clarify t...

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Autores principales: Wang, Hao, Dong, Lin, Qu, Fangfei, He, Huimin, Sun, Wei, Man, Yuqing, Jiang, Hongjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178892/
https://www.ncbi.nlm.nih.gov/pubmed/32298152
http://dx.doi.org/10.1080/13880209.2020.1751661
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author Wang, Hao
Dong, Lin
Qu, Fangfei
He, Huimin
Sun, Wei
Man, Yuqing
Jiang, Hongjie
author_facet Wang, Hao
Dong, Lin
Qu, Fangfei
He, Huimin
Sun, Wei
Man, Yuqing
Jiang, Hongjie
author_sort Wang, Hao
collection PubMed
description CONTEXT: Both nobiletin (NBL) and glycyrrhizin (GL) have anti-inflammatory and antitumor properties. These agents may be co-administered in the clinic. However, the drug–drug interaction between them is not clear. OBJECTIVE: The drug–drug interaction between GL and NBL was investigated, to clarify the effect of GL on the pharmacokinetics of NBL, and its main mechanism. MATERIALS AND METHODS: The pharmacokinetic profiles of oral administration of NBL (50 mg/kg) in Sprague-Dawley rats of two groups with six each, with or without pre-treatment of GL (100 mg/kg/day for 7 days), were investigated. The effects of GL on the metabolic stability and transport of NBL were also investigated through the rat liver microsome and Caco-2 cell transwell models. RESULTS: The results showed that GL significantly decreased the peak plasma concentration (from 1.74 ± 0.15 to 1.12 ± 0.10 μg/mL) and the t(1/2) (7.44 ± 0.65 vs. 5.92 ± 0.68) of NBL, and the intrinsic clearance rate of NBL was increased by the pre-treatment with GL (39.49 ± 2.5 vs. 48.29 ± 3.4 μL/min/mg protein). The Caco-2 cell transwell experiments indicated that GL could increase the efflux ratio of NBL from 1.61 to 2.41. DISCUSSION AND CONCLUSION: These results indicated that GL could change the pharmacokinetic profile of NBL, via increasing the metabolism and efflux of NBL in rats. It also suggested that the dose of NBL should be adjusted when co-administrated with GL in the clinic.
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spelling pubmed-71788922020-05-01 Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism Wang, Hao Dong, Lin Qu, Fangfei He, Huimin Sun, Wei Man, Yuqing Jiang, Hongjie Pharm Biol Research Article CONTEXT: Both nobiletin (NBL) and glycyrrhizin (GL) have anti-inflammatory and antitumor properties. These agents may be co-administered in the clinic. However, the drug–drug interaction between them is not clear. OBJECTIVE: The drug–drug interaction between GL and NBL was investigated, to clarify the effect of GL on the pharmacokinetics of NBL, and its main mechanism. MATERIALS AND METHODS: The pharmacokinetic profiles of oral administration of NBL (50 mg/kg) in Sprague-Dawley rats of two groups with six each, with or without pre-treatment of GL (100 mg/kg/day for 7 days), were investigated. The effects of GL on the metabolic stability and transport of NBL were also investigated through the rat liver microsome and Caco-2 cell transwell models. RESULTS: The results showed that GL significantly decreased the peak plasma concentration (from 1.74 ± 0.15 to 1.12 ± 0.10 μg/mL) and the t(1/2) (7.44 ± 0.65 vs. 5.92 ± 0.68) of NBL, and the intrinsic clearance rate of NBL was increased by the pre-treatment with GL (39.49 ± 2.5 vs. 48.29 ± 3.4 μL/min/mg protein). The Caco-2 cell transwell experiments indicated that GL could increase the efflux ratio of NBL from 1.61 to 2.41. DISCUSSION AND CONCLUSION: These results indicated that GL could change the pharmacokinetic profile of NBL, via increasing the metabolism and efflux of NBL in rats. It also suggested that the dose of NBL should be adjusted when co-administrated with GL in the clinic. Taylor & Francis 2020-04-16 /pmc/articles/PMC7178892/ /pubmed/32298152 http://dx.doi.org/10.1080/13880209.2020.1751661 Text en © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Hao
Dong, Lin
Qu, Fangfei
He, Huimin
Sun, Wei
Man, Yuqing
Jiang, Hongjie
Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism
title Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism
title_full Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism
title_fullStr Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism
title_full_unstemmed Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism
title_short Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism
title_sort effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178892/
https://www.ncbi.nlm.nih.gov/pubmed/32298152
http://dx.doi.org/10.1080/13880209.2020.1751661
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