Inhibition of antipyrine metabolite formation in rats<i>in vivo</i>

Abstract

The effect of four inhibitors of cytochrome P-450-mediated drug oxidations (SKF 525A, cimetidine, metyrapone and alpha-naphthoflavone) on the urinary metabolite pattern and 14CO2 exhalation rate (CER)-time profile following [N-methyl-14C]antipyrine administration has been investigated. The CER-time profiles indicated that inhibition of antipyrine metabolism was in the rank order SKF 525A greater than cimetidine greater than metyrapone greater than ANF. The urinary metabolite patterns showed selectively in action towards particular pathways, 3-hydroxylation being primarily decreased by SKF 525A and cimetidine, and N-demethylation by ANF. The results provide further evidence for involvement of multiple forms of cytochrome P-450 in antipyrine metabolism.