Comparative biochemical pharmacology of the oxicams.
The chronicity of the inflammatory process requires persistent tissue concentrations of non-steroidal 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, consequently, a lower incidence of adverse reactions at these target organs. 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.
Fenner
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F. Hoffmann-La Roche & Co. Ltd., Basel, Switzerland.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism* / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D010894:Piroxicam / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000378:metabolism; D011485:Protein Binding
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D011448:Prostaglandin Antagonists; D010894:Piroxicam; C013580:isoxicam; C032801:tenoxicam