Metabolism of piroxicam by laboratory animals

Piroxicam, a potent new nonsteroidal antiinflammatory agent, was radiolabeled in a biologically stable position by tritium exchange and administered at doses of 20 mg/kg to the rat, dog, and rhesus monkey. Metabolites were isolated from excreta by chromatographic methods and identified by their mass spectra and by comparison with authentic samples. Piroxicam is metabolized by cyclodehydration, by hydroxylation on the pyridyl moiety, and by a sequence of reactions involving amide hydrolysis, decarboxylation, ring contraction, and N-demethylation. In the rat, piroxicam is also metabolized by hydroxylation in two positions on the benzothiazine nucleus.