Risk-Benefit Assessment of Ethinylestradiol Using a Physiologically Based Pharmacokinetic Modeling Approach.

ABSTRACT: Current formulations of combined oral contraceptives (COC) containing ethinylestradiol (EE) have ≤35 μg due to increased risks of cardiovascular diseases (CVD) with higher doses of EE. Low-dose formulations however, have resulted in increased incidences of breakthrough bleeding and contraceptive failure, particularly when coadministered with inducers of cytochrome P450 enzymes (CYP). The developed physiologically based pharmacokinetic model quantitatively predicted the effect of CYP3A4 inhibition and induction on the pharmacokinetics of EE. The predicted C_max and AUC ratios when coadministered with voriconazole, fluconazole, rifampicin, and carbamazepine were within 1.25 of the observed data. Based on published clinical data, an AUC_ss value of 1,000 pg/ml.h was select

SUBMITTER: Ezuruike U 

PROVIDER: S-EPMC6282492 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature