Isoxicam is a potent, orally active, nonsteroidal anti-inflammarory drug with prolonged activtiy in experimentally induced inflammation in rats. Isoxicam is less ulcerogenic, acutely less toxic and, therefore, appears to have a therapeutic ratio superior to other standard agents to which it was compared.
In the adrenalectomized rat placed on a regular diet, neither ammoniated glycyrrhizin nor licorice was able to prolong survival time beyond that of the controls while desoxycorticosterone acetate (DCA) was very effective. When adrenalectomized rats were maintained on saline, it was observed that only DCA caused significant polydipsia, arterial hypertension and cardiovascular lesions; ammoniated glycyrrhizin and licorice were practically inactive, in contrast to their previously reported activity in the normal rat. The presence of the adrenal glands appears necessary to the renal cardiovascular effects of these extracts and it seems that the observed activity is mediated through these glands and that neither ammoniated glycyrrhizin nor licorice possesses direct DCA-like or mineralocorticoid properties.
Unlike several arylacetic acid derivatives (indomethacin, fenoprofen, ibuprofen, flurbiprofen and naproxen), the anti-arthritic activity of isoxicam is not reduced in the adjuvant-induced polyarthritis assay by the concomitant administration of aspirin or D-propoxyphene.
Liver function alterations, in the adjuvant induced polyarthritis procedure in rats, has been demonstrated by many investigators. We observed a significant inhibition of the polyarthritis with phenylbutazone but we were unable to find any changes in the relative liver weights of SGPT, AP or BUN in polyarthritic or phenylbutazone treated rats. However, we did observe that polyarthritic rats maintained a significantly higher plasma phenylbutazone concentration than the corresponding non-arthritic controls. This appears to futher substantiate the influence of 'pathopharmacodynamics' on the disposition and activity of drugs.
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