Naproxen sodium (Anaprox): pharmacology, pharmacokinetics and drug interactions

Naproxen sodium (Anaprox) is a potent antiinflammatory and analgesic agent. The drug has demonstrated a variety of biologic actions, including stabilization of lysosomal membranes, but most of its therapeutic activity is probably mediated through prostaglandin synthesis inhibition. The linkage between inhibition of prostaglandin synthesis and relief of dysmenorrhea has been documented in clinical studies, reported elsewhere in this supplement. Of relevance is the selective activity of naproxen sodium on uterine microsomal preparations. Once dissolved in biologic fluids, naproxen and naproxen sodium are chemically identical species and have the same biologic properties. Administration of naproxen as the sodium salt (Anaprox), however, permits more rapid absorption from the gastrointestinal tract. In either form, the drug is essentially completely absorbed. Its metabolic half-life averages 13 hours. The metabolism of naproxen is quite simple: it is excreted almost entirely in the urine as the native molecule, its oxidative 6-desmethyl metabolite and their respective conjugates. Naproxen is an acidic drug that is highly bound to plasma albumin. It may thus be expected to displace and transiently increase the tissue availability of other protein-bound drugs. In practice, however, potential interactions with both warfarin and tolbutamide have been evaluated and do not appear to be of clinical significance. Naproxen has a high therapeutic index and a shallow dose-response curve, so the effect of other drugs on its pharmacokinetics is not likely to have a large clinical impact.