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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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Detalles Bibliográficos
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
Descripción
Sumario: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.