Pharmacokinetics and Anti-Gastric Ulceration Activity of Oral Administration of Aceclofenac and Esomeprazole in Rats
| Autor: | Sang-Min Cho, Seung Eun Chung, Subindra Kazi Thapa, Soyoung Shin, Tae Hwan Kim, Youn-Woong Choi, Won-ho Kang, Da Young Lee, Hyeon Myeong Jeong, Chang Ho Song, Kyu-Yeol Nam, Beom Soo Shin, Jun Young Lim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Metabolite
lcsh:RS1-441 Pharmaceutical Science Pharmacology Article Esomeprazole lcsh:Pharmacy and materia medica 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Diclofenac Pharmacokinetics Oral administration esomeprazole aceclofenac medicine 030203 arthritis & rheumatology business.industry gastric ulcer Stomach Bioavailability diclofenac medicine.anatomical_structure chemistry Aceclofenac 030211 gastroenterology & hepatology business pharmacokinetics medicine.drug |
| Zdroj: | Pharmaceutics Volume 10 Issue 3 Pharmaceutics, Vol 10, Iss 3, p 152 (2018) |
| ISSN: | 1999-4923 |
| DOI: | 10.3390/pharmaceutics10030152 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |