Bioavailability and absorption characteristics of naproxen sodium have been shown to be superior to that of naproxen in tablet formulations. In this study naproxen sodium suppositories were compared with naproxen tablets and naproxen suppositories with respect to plasma concentrations and bioavailability of naproxen. Eleven healthy volunteers participated in a randomized crossover study comparing naproxen sodium suppositories (equivalent to 500 mg naproxen) and naproxen suppositories (500 mg). Tmax (1.4 h) was significantly shorter after the administration of naproxen sodium suppositories than after naproxen tablets (2.4 h), whereas Cmax was higher after the tablet formulation. No difference was observed with respect to bioavailability and biologic half-life of naproxen. In a second crossover study in six volunteers suppositories containing either naproxen sodium or naproxen were compared. Tmax was shorter and Cmax significantly higher after administration of the sodium naproxen suppository formulation. The sodium naproxen suppositories were well tolerated and proved to be a safe and reliable way of administering naproxen, giving therapeutic naproxen concentrations within the 1st h after administration.