This study examined the effects of esomeprazole on aceclofenac pharmacokinetics and\ngastrointestinal complications in rats. Aceclofenac alone, or in combination with esomeprazole,\nwas orally administered to male Sprague-Dawley rats. Plasma concentrations of aceclofenac,\nits major metabolite diclofenac, and esomeprazole were simultaneously determined by a novel liquid\nchromatography-tandem mass spectrometry method. Gastrointestinal damage was determined by\nmeasuring ulcer area and ulcer lesion index of the stomach. Oral administration of aceclofenac\ninduced significant gastric ulceration, which was inhibited by esomeprazole administration.\nFollowing concurrent administration of aceclofenac and esomeprazole, overall pharmacokinetic\nprofiles of aceclofenac and metabolic conversion to diclofenac were unaffected by esomeprazole.\nAceclofenac metabolism and pharmacokinetics were not subject to significant food effects, whereas\nbioavailability of esomeprazole decreased in fed compared to fasting conditions. In contrast,\nthe pharmacokinetics of aceclofenac and esomeprazole were significantly altered by different dosing\nvehicles. These results suggest that co-administration of esomeprazole with aceclofenac may reduce\naceclofenac-induced gastrointestinal complications without significant pharmacokinetic interactions.\nThe optimal combination and clinical significance of the benefits of the combination of aceclofenac\nand esomeprazole need to be further evaluated.
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