Pharmacokinetic Comparison Study of a Combination Containing 500 mg of Naproxen and 20 mg of Esomeprazole: A Randomized, Single-dose, 2-way Crossover, Open-label Study in Healthy Korean Men

Purpose: Nonsteroidal anti-inflammatory drugs have been used for analgesic, anti-inflammatory, and antithrombotic effects, but they carry a risk of major gastrointestinal damage. This risk can be greatly reduced by the coadministration of inhibitors of gastric acid secretion, such as proton pump inhibitors. This study was performed for the subsequent marketing of a combination drug that contained 500 mg of naproxen and 20 mg of esomeprazole in Korea. We evaluated the comparative bioavailability and tolerability of the test and reference formulations in healthy men. Methods: A total of 60 healthy men were enrolled in this single-dose, randomized, open-label, 2-period, 2-sequence, crossover study. During each period, men received a combination of 500 mg of naproxen and 20 mg of esomeprazole for test or reference, and between each period, there was a 1-week washout period. Blood samples were obtained 21 times throughout each period before dosing and 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 48, and 72 hours after oral administration. Plasma concentrations were determined using LC-MS/MS. The pharmacokinetic parameters, including C-max, AUC(0-t), AUC(0-infinity), and T-max, were measured, and all treatment-emergent adverse events and their associations with the study medications were recorded throughout the entire study. Findings: A total of 59 men completed the study. No significant differences were found in the prevalence of AEs between the 2 formulations. In addition, there were no serious or unexpected AEs during the study. Both formulations had very similar C-max, AUC, and t(1/2) values, but the T-max of naproxen appeared earlier in the test formulation than in the reference formulation and that of esomeprazole appeared later in the test formulation than in the reference formulation. Implications: This study suggests that the test and reference formulations of a combination of 500 mg of naproxen and 20 mg of esomeprazole are bioequivalent in the extent of absorption and peak concentration. We anticipate that the test formulation will treat those who need relief from pain and inflammation and will decrease the risk of developing gastric ulcers. (C) 2015 Elsevier HS Journals, Inc. All rights reserved.