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Naproxen (NPX) is chemically known as (+)-(S)-2-(6-methoxynaphthalen-2-yl) propanoic acid, which is used as a nonsteroidal anti-inflammatory drug (NSAID). It is commonly used for relief of a wide variety of pain, fever, inflammations and stiffness arises from various physiological disorders such as osteoarthritis, rheumatoid arthritis, psoriatic arthritis, migraine, gout, kidney stones, menstrual cramps, tendinitis, bursitis, etc. NPX has potential capability of causing ulcers and stomach bleeding just like other nonselective COX2 inhibitors. Therefore, it is pharmacologically rational to give any acid-suppressing agent concurrently with NPX. Traditionally, proton pump inhibitors (PPIs) have become a drug of choice in this case. Among several PPIs, esomeprazole (ESP), the S-isomer of omeprazole, is extensively used during treatment with NPX due to the fact that ESP provides more effective acid control than omeprazole, with reduced interpatient variability, thereby offering the potential for improved efficacy in acid-related diseases.