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Pharmacokinetics and Anti-Gastric Ulceration Activity of Oral Administration of Aceclofenac and Esomeprazole in Rats
This study examined the effects of esomeprazole on aceclofenac pharmacokinetics and gastrointestinal complications in rats. Aceclofenac alone, or in combination with esomeprazole, was orally administered to male Sprague-Dawley rats. Plasma concentrations of aceclofenac, its major metabolite diclofen...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160962/ https://www.ncbi.nlm.nih.gov/pubmed/30200587 http://dx.doi.org/10.3390/pharmaceutics10030152 |
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author | Kim, Tae Hwan Thapa, Subindra Kazi Lee, Da Young Chung, Seung Eun Lim, Jun Young Jeong, Hyeon Myeong Song, Chang Ho Choi, Youn-Woong Cho, Sang-Min Nam, Kyu-Yeol Kang, Won-Ho Shin, Soyoung Shin, Beom Soo |
author_facet | Kim, Tae Hwan Thapa, Subindra Kazi Lee, Da Young Chung, Seung Eun Lim, Jun Young Jeong, Hyeon Myeong Song, Chang Ho Choi, Youn-Woong Cho, Sang-Min Nam, Kyu-Yeol Kang, Won-Ho Shin, Soyoung Shin, Beom Soo |
author_sort | Kim, Tae Hwan |
collection | PubMed |
description | This study examined the effects of esomeprazole on aceclofenac pharmacokinetics and gastrointestinal complications in rats. Aceclofenac alone, or in combination with esomeprazole, was orally administered to male Sprague-Dawley rats. Plasma concentrations of aceclofenac, its major metabolite diclofenac, and esomeprazole were simultaneously determined by a novel liquid chromatography-tandem mass spectrometry method. Gastrointestinal damage was determined by measuring ulcer area and ulcer lesion index of the stomach. Oral administration of aceclofenac induced significant gastric ulceration, which was inhibited by esomeprazole administration. Following concurrent administration of aceclofenac and esomeprazole, overall pharmacokinetic profiles of aceclofenac and metabolic conversion to diclofenac were unaffected by esomeprazole. Aceclofenac metabolism and pharmacokinetics were not subject to significant food effects, whereas bioavailability of esomeprazole decreased in fed compared to fasting conditions. In contrast, the pharmacokinetics of aceclofenac and esomeprazole were significantly altered by different dosing vehicles. These results suggest that co-administration of esomeprazole with aceclofenac may reduce aceclofenac-induced gastrointestinal complications without significant pharmacokinetic interactions. The optimal combination and clinical significance of the benefits of the combination of aceclofenac and esomeprazole need to be further evaluated. |
format | Online Article Text |
id | pubmed-6160962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61609622018-10-01 Pharmacokinetics and Anti-Gastric Ulceration Activity of Oral Administration of Aceclofenac and Esomeprazole in Rats Kim, Tae Hwan Thapa, Subindra Kazi Lee, Da Young Chung, Seung Eun Lim, Jun Young Jeong, Hyeon Myeong Song, Chang Ho Choi, Youn-Woong Cho, Sang-Min Nam, Kyu-Yeol Kang, Won-Ho Shin, Soyoung Shin, Beom Soo Pharmaceutics Article This study examined the effects of esomeprazole on aceclofenac pharmacokinetics and gastrointestinal complications in rats. Aceclofenac alone, or in combination with esomeprazole, was orally administered to male Sprague-Dawley rats. Plasma concentrations of aceclofenac, its major metabolite diclofenac, and esomeprazole were simultaneously determined by a novel liquid chromatography-tandem mass spectrometry method. Gastrointestinal damage was determined by measuring ulcer area and ulcer lesion index of the stomach. Oral administration of aceclofenac induced significant gastric ulceration, which was inhibited by esomeprazole administration. Following concurrent administration of aceclofenac and esomeprazole, overall pharmacokinetic profiles of aceclofenac and metabolic conversion to diclofenac were unaffected by esomeprazole. Aceclofenac metabolism and pharmacokinetics were not subject to significant food effects, whereas bioavailability of esomeprazole decreased in fed compared to fasting conditions. In contrast, the pharmacokinetics of aceclofenac and esomeprazole were significantly altered by different dosing vehicles. These results suggest that co-administration of esomeprazole with aceclofenac may reduce aceclofenac-induced gastrointestinal complications without significant pharmacokinetic interactions. The optimal combination and clinical significance of the benefits of the combination of aceclofenac and esomeprazole need to be further evaluated. MDPI 2018-09-06 /pmc/articles/PMC6160962/ /pubmed/30200587 http://dx.doi.org/10.3390/pharmaceutics10030152 Text en © 2018 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kim, Tae Hwan Thapa, Subindra Kazi Lee, Da Young Chung, Seung Eun Lim, Jun Young Jeong, Hyeon Myeong Song, Chang Ho Choi, Youn-Woong Cho, Sang-Min Nam, Kyu-Yeol Kang, Won-Ho Shin, Soyoung Shin, Beom Soo Pharmacokinetics and Anti-Gastric Ulceration Activity of Oral Administration of Aceclofenac and Esomeprazole in Rats |
title | Pharmacokinetics and Anti-Gastric Ulceration Activity of Oral Administration of Aceclofenac and Esomeprazole in Rats |
title_full | Pharmacokinetics and Anti-Gastric Ulceration Activity of Oral Administration of Aceclofenac and Esomeprazole in Rats |
title_fullStr | Pharmacokinetics and Anti-Gastric Ulceration Activity of Oral Administration of Aceclofenac and Esomeprazole in Rats |
title_full_unstemmed | Pharmacokinetics and Anti-Gastric Ulceration Activity of Oral Administration of Aceclofenac and Esomeprazole in Rats |
title_short | Pharmacokinetics and Anti-Gastric Ulceration Activity of Oral Administration of Aceclofenac and Esomeprazole in Rats |
title_sort | pharmacokinetics and anti-gastric ulceration activity of oral administration of aceclofenac and esomeprazole in rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160962/ https://www.ncbi.nlm.nih.gov/pubmed/30200587 http://dx.doi.org/10.3390/pharmaceutics10030152 |
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