ArticleThe AAPS journal2025
Investigating Sulfotransferase Mediated Drug Interactions of Ethinylestradiol using a Physiologically Based Pharmacokinetic Model.
Article in The AAPS journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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9 authors.
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Abstract
Ethinylestradiol (EE) is a common estrogen used in combined oral contraceptives. CYP3A4 and SULT1E1 are the major enzymes that metabolize EE, while CYP2C9 and UGT1A1 have minor contributions. Drug-drug interactions (DDIs) mediated by inhibition or induction of metabolism can adversely impact the safety and efficacy of EE. A physiologically-based pharmacokinetic (PBPK) model was previously developed and extensively verified to predict CYP3A4-mediated DDIs of EE. Recent clinical evidence showed increased EE exposure following coadministration with the SULT1E1 inhibitors etoricoxib and ziritaxestat, highlighting the need to expand the PBPK model to allow for predictions of SULT1E1-mediated DDIs. A PBPK model including SULT metabolism of EE was constructed and the interactions with PBPK models developed for etoricoxib and ziritaxestat were simulated. The observed EE concentrations were within the simulated 95% percentiles for the control and the DDI scenario. The predicted ratios for peak concentration (C
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