Oxidation of tenoxicam by leukocyte peroxidases and H2O2 produces novel products.

A leukocyte extract, which had a high peroxidase activity (mostly myeloperoxidase), converted tenoxicam [4-hydroxy-N-(2'-pyridyl)-2-methyl-2H-thieno-(2,3e)-1,2-thiazine-3 - carboxamide-1,1-dioxide] a potent antiinflammatory drug, into four novel metabolites in the presence of H2O2: 4,5-dihydro-4-oxo-5-methyliminopyrido (1,2a) imidazole (metabolite I), 2-carboxyl-3-thiofenesulfinic acid (metabolite II), 2-carboxyl-3-thiofenesulfonic acid (metabolite III), and N-methyl-N'-(2-pyridyl)oxamide (metabolite IV). These metabolites were probably formed by a one-electron oxidation reaction at the center carbon atom of the beta-diketone moiety of tenoxicam. Tenoxicam is a cofactor for the reduction of peroxidases and this capability may explain at least a part of the antiinflammatory effect of tenoxicam.