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.

Desoxo-narchinol A is one of the major active constituents from Nardostachys jatamansi, which has been reported to possess various pharmacological activities, including anti-inflammatory, antioxidant, and anticonvulsant activity. A simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of desoxo-narchinol A in two different biological matrices, i.e., rat plasma and mouse plasma, using sildenafil as an internal standard (IS). The method involved simple protein precipitation with acetonitrile and the analyte was separated by gradient elution using 100% acetonitrile and 0.1% formic acid in water as a mobile phase. The MS detection was performed with a turbo electrospray in positive ion mode. The lower limit of quantification was 10 ng/mL in both rat and mouse plasma. Intra- and inter-day accuracies were in the ranges of 97.23–104.54% in the rat plasma and 95.90–110.11% in the mouse plasma. The precisions were within 8.65% and 6.46% in the rat and mouse plasma, respectively. The method was applied to examine the pharmacokinetics of desoxo-narchinol A, and the oral bioavailability of desoxo-narchinol A was 18.1% in rats and 28.4% in mice. The present results may be useful for further preclinical and clinical studies of desoxo-narchinol A.