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Overview of the pharmacological properties, pharmacokinetics and animal safety assessment of lornoxicam.

Lornoxicam is a new, highly potent antirheumatic agent which is an oxicam derivative. Although highly potent as a cyclo-oxygenase inhibitor, the compound does not cause inhibition of 5-lipoxygenase and does not appear to shunt arachidonic acid through this cascade. This powerful inhibition of cyclo-oxygenase has manifested itself as highly potent analgesic and anti-inflammatory effects in animal studies and also prevented the bone destruction which normally occurs in the adjuvant polyarthritic rat. To explain this finding, studies have demonstrated that lornoxicam inhibits polymorphonuclear (PMN)-leukocyte migration; inhibits the release of superoxide from human PMN-leukocytes; inhibits the release of platelet derived growth factor (PDGF) from human platelets and stimulates the synthesis of proteoglycans in cartilage in tissue culture. Lornoxicam is well absorbed and has a plasma t1/2 in man of 4 hours which is distinctly different from other oxicams. It is metabolized in animals and in man to the 5'-hydroxy-metabolite which is inactive in pharmacological tests. In vitro and in vivo animal safety studies have demonstrated both subchronically and chronically that lornoxicam manifests no unusual toxicity, is not a mutagen nor is it tumorigenic and causes no fetal teratogenicity in reproduction studies.