Fenner H
F. Hoffmann-La Roche & Co. Ltd., Basel, Switzerland.
Scand J Rheumatol Suppl. 1987;65:97-101. doi: 10.3109/03009748709102185.
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 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.
炎症过程的慢性化需要非甾体抗炎药（NSAIDs）在组织中持续保持一定浓度，通过使用半衰期长的药物并采用每日一次的给药方案可最佳地实现这一点。恶丙嗪被证明是最有前景的NSAIDs类别之一。它们具有相似的分子结构，不过用噻吩并噻嗪系统取代苯并噻嗪环赋予替诺昔康更具亲水性的特性。因此，替诺昔康的特点是进入需要更多亲脂性的组织（如中枢神经系统和皮肤）的渗透率较低，这可能解释了与亲脂性更强的NSAIDs相比，在这些靶器官中不良反应发生率较低的原因。由于游离部分小、与蛋白质紧密结合以及亲水性特性，替诺昔康向肝细胞的扩散较差，这解释了其低肝提取率以及——因此——长半衰期。与吲哚美辛和双氯芬酸相比，恶丙嗪对前列腺素的合成和释放具有中等抑制活性；替诺昔康的活性是吡罗昔康的一半，这反映了它们稳态血浆浓度的相应差异。
