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Naproxen Metabolism in Man

In summary, naproxen is an acidic, highly albumin-bound drug. After oral administration, it is promptly and fully absorbed. The mean half-life of the drug in man is 13 hours, close to ideal for twice-daily administration. The only metabolite detected in man is the 6-desmethyl compound. Both it and naproxen itself are excreted in the urine, primarily as conjugates. The kinetics of naproxen binding to serum albumin tend to limit attainable plasma levels. They increase little if the dose is increased beyond 500 mg twice daily, since greater concentrations are rapidly cleared. Albumin binding and competitive displacement are also responsible for potential interactions of naproxen with drugs such as warfarin, sulfonylureas, and aspirin. Experience thus far does not indicate that any of the potential interactions are clinically meaningful.