@article {Guengerich500, author = {F P Guengerich}, title = {Oxidation of 17 alpha-ethynylestradiol by human liver cytochrome P-450.}, volume = {33}, number = {5}, pages = {500--508}, year = {1988}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {One of the classic examples of adverse drug interactions involves pregnancies in women using the oral contraceptive 17 alpha-ethynylestradiol who also ingest rifampicin or barbiturates or hydantoins. Previous work had demonstrated increased metabolism (2-hydroxylation) of 17 alpha-ethynylestradiol in individuals using rifampicin. In this report evidence is presented for the involvement of a specific form of human cytochrome P-450, termed P-450NF, in this phenomenon. Although purified P-450NF has only relatively low catalytic 17 alpha-ethynylestradiol 2-hydroxylase activity, antibodies raised to P-450NF specifically inhibited greater than 90\% of the activity in liver microsomes which had either high or low catalytic activity. When different liver samples were compared, rates of microsomal 17 alpha-ethynylestradiol 2-hydroxylation were highly correlated with amounts of immunochemically measured P-450NF or rates of nifedipine oxidation, a characteristic activity of P-450NF. Prior incubation of human liver microsomes with NADPH and troleandomycin resulted in decreased 17 alpha-ethynylestradiol 2-hydroxylation. In addition, 17 alpha-ethynylestradiol appears to be a mechanism-based inhibitor in human liver microsomes, as shown by the loss of both spectrally detectable cytochrome P-450 and 17 alpha-ethynylestradiol 2-hydroxylase activity during incubation in the presence of NADPH. Additional experiments did not show any evidence for the involvement of a number of other human cytochrome P-450 enzymes in 17 alpha-ethynylestradiol 2-hydroxylation (i.e., P-450DB, P-450PA, P-450MP, P-450j). These results are consistent with the view that P-450NF is the major enzyme involved in 17 alpha-ethynylestradiol oxidation and that drugs and hormones which influence the expression and activity of this enzyme can influence the efficacy and side effects of this compound.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/33/5/500}, eprint = {https://molpharm.aspetjournals.org/content/33/5/500.full.pdf}, journal = {Molecular Pharmacology} }