Comparative Biochemical Pharmacology of the Oxicams

Abstract

The chronicity of the inflammatory process requires persistent tissue concentrations of nonsteroidal anti-inflammatory drugs (NSAIDs), best achieved by using a drug with a long half-life as a once-daily regimen.

The oxicams proved to be one of the most promising classes of NSAIDs. They have a similar molecular structure, though substitution of the benzothiazine ring by a thienothiazine system gives tenoxicam a more hydrophilic character. Tenoxicam is thus characterised by lower penetration into tissues requiring more lipophilic properties, e.g. the CNS and skin, and this may explain the lower incidence of adverse reactions at these target organs in comparison with more lipophilic NSAIDs. Poor diffusion into hepatic cells–as a result of a small free fraction, tight binding to proteins and hydrophilic character–explains its low hepatic extraction ratio and–as a consequence–a long half-life.

Compared to indomethacin and diclofenac, the oxicams have a moderate inhibitory activity on the synthesis and release of prostaglandins; tenoxicam is half as active as piroxicam, reflecting the correspondent difference in their steady-state plasma concentrations.