Lack of pharmacokinetic interaction between esomeprazole and the nonsteroidal anti-inflammatory drugs naproxen and rofecoxib in healthy subjects

Background: We investigated the potential interactions between esomeprazole and a non-selective nonsteroidal anti-inflammatory drug (NSAID; naproxen) or a cyclo-oxygenase (COX)-2-selective NSAID (rofecoxib) in healthy subjects. Methods: Two studies of identical randomised, open, three-way crossover design were conducted. Subjects (n = 32 for both studies) were to receive I week's treatment with esomeprazole 40 mg once daily (studies A and B), naproxen 250 mg twice daily (study A), rofecoxib 12.5 mg once daily (study 13), and esomeprazole in combination with naproxen (study A) or rofecoxib (study B). Study periods were separated by a 2-week washout period. Results: On day 7 of dosing, the ratios (and 95% CIs) for the area under the plasma concentration-time curve during the dosing interval (AUC(tau)) and observed maximum plasma concentration (C-max) of esomeprazole and NSAID combination/NSAID alone were 0.98 (0.94, 1.01) and 1.00 (0.97, 1.04), respectively, for study A, and 1.15 (1.06, 1.24) and 1.14 (1.02, 1.28), respectively, for study B. The ratios (and 95% CIs) for AUC(tau) and C-max of esomeprazole and NSAID combination/esomeprazole alone were 0.96 (0.89, 1.03) and 0.92 (0.85, 1.00), respectively, for study A, and 1.05 (0.96, 1.15) and 1.05 (0.94, 1.18), respectively, for study B. All treatments were well tolerated during the study period. Conclusion: Naproxen and rofecoxib do not interact with esomeprazole, and esomeprazole does not affect the pharmacokinetics of naproxen or rofecoxib. These findings indicate that esomeprazole can be used in combination with NSAIDs without the risk of a pharmacokinetic interaction.