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.
Ichihara
S
S
Department of Drug Metabolism, Nippon Roche Research Center, Kanagawa, Japan.
Tomisawa
H
H
Fukazawa
H
H
Tateishi
M
M
Joly
R
R
Heintz
R
R
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007962:Leukocytes / Q000201:enzymology* / Q000378:metabolism; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D010894:Piroxicam / Q000031:analogs & derivatives* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010894:Piroxicam; D006861:Hydrogen Peroxide; D010544:Peroxidases; C032801:tenoxicam