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Effects of diclofenac on the pharmacokinetics of celastrol in rats and its transport

Context: Diclofenac and celastrol are always used together for the treatment of rheumatoid arthritis; the herb–drug interaction potential between diclofenac and celastrol is still unknown. Objective: This study investigates the effects of diclofenac on the pharmacokinetics of celastrol in rats. Mate...

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Autores principales: Wang, Zengfu, Chen, Dali, Wang, Zhongwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130456/
https://www.ncbi.nlm.nih.gov/pubmed/29651912
http://dx.doi.org/10.1080/13880209.2018.1459740
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author Wang, Zengfu
Chen, Dali
Wang, Zhongwei
author_facet Wang, Zengfu
Chen, Dali
Wang, Zhongwei
author_sort Wang, Zengfu
collection PubMed
description Context: Diclofenac and celastrol are always used together for the treatment of rheumatoid arthritis; the herb–drug interaction potential between diclofenac and celastrol is still unknown. Objective: This study investigates the effects of diclofenac on the pharmacokinetics of celastrol in rats. Materials and methods: Twelve male Sprague-Dawley rats were divided into two groups and received celastrol (1 mg/kg) or both celastrol (1 mg/kg) and diclofenac (10 mg/kg) by oral gavage, and blood samples were collected via the oculi chorioideae vein and determined using the LC-MS method developed in this study. Additionally, the effects of diclofenac on the transport of celastrol were investigated using a Caco-2 cell transwell model. Results: Diclofenac could significantly (p < 0.05) decrease the C(max) (from 66.93 ± 10.28 to 41.25 ± 8.06 ng/mL) and AUC(0-t) (from 765.84 ± 163.61 to 451.33 ± 110.88 μg × h/L) of celastrol in rats. The efflux ratio of celastrol increased significantly (p < 0.05) from 3.12 to 4.55 with the treatment of diclofenac. Discussion and conclusion: These results indicated that diclofenac could decrease the system exposure of celastrol in rats when they are co-administered, and these effects might be exerted via decreasing its absorption in intestine.
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spelling pubmed-61304562018-09-27 Effects of diclofenac on the pharmacokinetics of celastrol in rats and its transport Wang, Zengfu Chen, Dali Wang, Zhongwei Pharm Biol Research Article Context: Diclofenac and celastrol are always used together for the treatment of rheumatoid arthritis; the herb–drug interaction potential between diclofenac and celastrol is still unknown. Objective: This study investigates the effects of diclofenac on the pharmacokinetics of celastrol in rats. Materials and methods: Twelve male Sprague-Dawley rats were divided into two groups and received celastrol (1 mg/kg) or both celastrol (1 mg/kg) and diclofenac (10 mg/kg) by oral gavage, and blood samples were collected via the oculi chorioideae vein and determined using the LC-MS method developed in this study. Additionally, the effects of diclofenac on the transport of celastrol were investigated using a Caco-2 cell transwell model. Results: Diclofenac could significantly (p < 0.05) decrease the C(max) (from 66.93 ± 10.28 to 41.25 ± 8.06 ng/mL) and AUC(0-t) (from 765.84 ± 163.61 to 451.33 ± 110.88 μg × h/L) of celastrol in rats. The efflux ratio of celastrol increased significantly (p < 0.05) from 3.12 to 4.55 with the treatment of diclofenac. Discussion and conclusion: These results indicated that diclofenac could decrease the system exposure of celastrol in rats when they are co-administered, and these effects might be exerted via decreasing its absorption in intestine. Taylor & Francis 2018-04-13 /pmc/articles/PMC6130456/ /pubmed/29651912 http://dx.doi.org/10.1080/13880209.2018.1459740 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://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/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Zengfu
Chen, Dali
Wang, Zhongwei
Effects of diclofenac on the pharmacokinetics of celastrol in rats and its transport
title Effects of diclofenac on the pharmacokinetics of celastrol in rats and its transport
title_full Effects of diclofenac on the pharmacokinetics of celastrol in rats and its transport
title_fullStr Effects of diclofenac on the pharmacokinetics of celastrol in rats and its transport
title_full_unstemmed Effects of diclofenac on the pharmacokinetics of celastrol in rats and its transport
title_short Effects of diclofenac on the pharmacokinetics of celastrol in rats and its transport
title_sort effects of diclofenac on the pharmacokinetics of celastrol in rats and its transport
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130456/
https://www.ncbi.nlm.nih.gov/pubmed/29651912
http://dx.doi.org/10.1080/13880209.2018.1459740
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