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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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.
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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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