The involvement of CYP3A4 and CYP2C9 in the metabolism of 17 alpha-ethinylestradiol.

Article Details

Citation

Wang B, Sanchez RI, Franklin RB, Evans DC, Huskey SE

The involvement of CYP3A4 and CYP2C9 in the metabolism of 17 alpha-ethinylestradiol.

Drug Metab Dispos. 2004 Nov;32(11):1209-12. Epub 2004 Aug 10.

PubMed ID
15304426 [ View in PubMed
]
Abstract

The role of specific cytochrome P450 (P450) isoforms in the metabolism of ethinylestradiol (EE) was evaluated. The recombinant human P450 isozymes CYP1A1, CYP1A2, CYP2C9, CYP2C19, and CYP3A4 were found to be capable of catalyzing the metabolism of EE (1 microM). Without exception, the major metabolite was 2-hydroxy-EE. The highest catalytic efficiency (Vmax/Km) was observed with rCYP1A1, followed by rCYP3A4, rCYP2C9, and rCYP1A2. The P450 isoforms 3A4 and 2C9 were shown to play a significant role in the formation of 2-hydroxy-EE in a pool of human liver microsomes by using isoform-specific monoclonal antibodies, in which the inhibition of formation was approximately 54 and 24%, respectively. The involvement of CYP3A4 and CYP2C9 was further confirmed by using selective chemical inhibitors (i.e., ketoconazole and sulfaphenazole). The relative contribution of each P450 isoform to the 2-hydroxylation pathway was obtained from the catalytic efficiency of each isoform normalized by its relative abundance in the same pool of human liver microsomes, as determined by quantitative Western blot analysis. Collectively, these results suggested that multiple P450 isoforms were involved in the oxidative metabolism of EE in human liver microsomes, with CYP3A4 and CYP2C9 as the major contributing enzymes.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
EthinylestradiolCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
Drug Interactions
DrugsInteraction
Ethinylestradiol
Rufinamide
The therapeutic efficacy of Ethinylestradiol can be decreased when used in combination with Rufinamide.