In vitro metabolism of isoxicam by horseradish peroxidase

Abstract

1. Disposition studies in vivo in animals and man indicate that hydroxylation of the isoxazole methyl group of isoxicam is the major route of metabolism.

2. Recently, N-methylsaccharin, saccharin, and an open-ring sulphonamide have been identified as additional isoxicam metabolites.

3. Attempts to form these metabolites in vitro with hepatic microsomal incubations were unsuccessful. However, incubations of isoxicam with purified horseradish peroxidase resulted in the formation of N-methylsaccharin and the open-ring sulphonamide in good overall yield (28% in 1 h).

4. A possible mechanism for HP-catalysed conversion of isoxicam to N-methylsaccharin and open-ring sulphonamide is presented.