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Abstract
1. The effect of four inhibitors of cytochrome P-450-mediated drug oxidations (SKF 52SA, cimetidine, metyrapone and α-naphthoflavone) on the urinary metabolite pattern and 14CO2 exhalation rate (CER)-time profile following [N-methyl-14C]antipyrine administration has been investigated.
2. The CER-time profiles indicated that inhibition of antipyrine metabolism was in the rank order SKF 525A >cimetidine > metyrapone >ANF.
3. The urinary metabolite patterns showed selectivity 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.