Pharmacokinetic Drug Interactions Involving 17α-Ethinylestradiol

@article{Zhang2007PharmacokineticDI,
  title={Pharmacokinetic Drug Interactions Involving 17$\alpha$-Ethinylestradiol},
  author={Hongjiang Zhang and Donghui Cui and Bonnie Wang and Yong-Hae Han and Praveen V. Balimane and Zheng Yang and Michael A. Sinz and A. David Rodrigues},
  journal={Clinical Pharmacokinetics},
  year={2007},
  volume={46},
  pages={133-157}
}
Abstract17α-Ethinylestradiol (EE) is widely used as the estrogenic component of oral contraceptives (OC). In vitro and in vivo metabolism studies indicate that EE is extensively metabolised, primarily via intestinal sulfation and hepatic oxidation, glucuronidation and sulfation. Cytochrome P450 (CYP)3A4-mediated EE 2-hydroxylation is the major pathway of oxidative metabolism of EE. For some time it has been known that inducers of drug-metabolising enzymes (such as the CYP3A4 inducer rifampicin… Expand
Drug Interactions Involving 17α-Ethinylestradiol: Considerations Beyond Cytochrome P450 3A Induction and Inhibition.
  • A David Rodrigues
  • Medicine
  • Clinical pharmacology and therapeutics
  • 2021
TLDR
It is widely acknowledged that drug-drug interactions (DDI) involving estrogen (17α-ethinylestradiol, EE)-containing oral contraceptives (OC) are important, and it is important to assess its projected (pre-Phase 1) or known therapeutic index and pharmacokinetic profile to enable the prioritization, design, and interpretation of NME-OC DDI studies. Expand
Efflux Transport Is an Important Determinant of Ethinylestradiol Glucuronide and Ethinylestradiol Sulfate Pharmacokinetics
TLDR
Altered efflux transport resulted in major alterations of EEG and EES pharmacokinetics, highlighting transport as a potential site of DDIs with EE conjugates. Expand
Role of rat cytochromes P450 in the oxidation of 17α-ethinylestradiol.
TLDR
The results demonstrate that EE2 is hydroxylated by several rat CYPs, among them CYP2C6 and 2C11 are most efficient in 2-hydroxy-EE2 formation, while CYP1A and 3A catalyze EE2 hydroxyation to the second product. Expand
Risk–Benefit Assessment of Ethinylestradiol Using a Physiologically Based Pharmacokinetic Modeling Approach
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The developed physiologically based pharmacokinetic model quantitatively predicted the effect of CYP3A4 inhibition and induction on the pharmacokinetics of EE and identified percentages of the population at risk of breakthrough bleeding alone and with varying degrees of CyP modulation. Expand
Effect of the ethinylestradiol/levonorgestrel combined oral contraceptive on the activity of cytochrome P4503A in obese women.
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Simeprevir is an NS3/4A protease inhibitor approved for the treatment of hepatitis C infection, as a component of combination therapy and does not have a clinically relevant effect on the pharmacokinetics of rilpivirine, tacrolimus, oral contraceptives and several other drugs metabolized by CYP enzymes. Expand
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TLDR
The results presented here indicate that estradiol derivatives down-regulate CYP2C19 expression via estrogen receptor (ER) α, which interacts with the newly identified ER-binding half site [estrogen response element (ERE)] at the position −151/−147 in the CYP1C19 promoter. Expand
Transporter Studies with the 3-O-Sulfate Conjugate of 17α-Ethinylestradiol: Assessment of Human Kidney Drug Transporters
TLDR
It is hypothesize that EE2-Sul is taken up into renal proximal tubule cells by OAT3, and OAT4 plays a role in its secretion into the renal brush border lumen. Expand
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References

SHOWING 1-10 OF 193 REFERENCES
Effects of the Antifungal Agents on Oxidative Drug Metabolism
TLDR
The interactions of ketoconazole with cyclosporin and tacrolimus have been applied for therapeutic purposes to allow a lower dosage and cost of the immunosuppressant and a reduced risk of fungal infections. Expand
Examination of 209 Drugs for Inhibition of Cytochrome P450 2C8
TLDR
An in vitro assessment of 209 frequently prescribed drugs and related xenobiotics was carried out to examine their potential to inhibit CYP2C8, and montelukast was identified as being of concern as a potential inhibitor of clinical relevance. Expand
Metabolism of 17 α-ethynylestradiol in humans
17 alpha-Ethynylestradiol is extensively sulfated but the sulfate is thought to primarily be a storage form of this estrogen. 2-Hydroxylation is clearly the major oxidative reaction, and theExpand
Pharmacokinetics of ethynyloestradiol in humans.
  • K. Fotherby
  • Medicine
  • Methods and findings in experimental and clinical pharmacology
  • 1982
TLDR
In women with a low bioavailability and short half-life for the steroid, its efficacy may be reduced and if not sufficiently to lose contraception value it may result in an increase in other side effects such as spotting. Expand
Effects of cytochrome P450 inducers on 17alpha-ethinyloestradiol (EE2) conjugation by primary human hepatocytes.
TLDR
The data indicate that the major EE2 metabolic products formed by human hepatocytes in vitro are direct EE2 conjugates with EE2 oxidation representing minor pathways, and the first observation of sulphotransferase induction by rifampicin in human hepatocyte in vitro resulting in increased [3H]-EE2 sulphation. Expand
Oxidation of 17 alpha-ethynylestradiol by human liver cytochrome P-450.
TLDR
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. Expand
THE INVOLVEMENT OF CYP3A4 AND CYP2C9 IN THE METABOLISM OF 17α-ETHINYLESTRADIOL
TLDR
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. Expand
Ethynylestradiol-mediated induction of hepatic CYP3A9 in female rats: implication for cyclosporine metabolism.
TLDR
Findings support the notion that the increased CyA-metabolizing capacity of EE(2)-treated female rat liver microsomes is due to the induction of the CYP3A9 enzyme. Expand
Pharmacokinetic Interactions with Rifampicin
TLDR
The antituberculosis drug rifampicin (rifampin) induces a number of drug-metabolising enzymes, having the greatest effects on the expression of cytochrome P450 (CYP) 3A4 in the liver and in the small intestine, which influences drug metabolism and transport. Expand
Induction of Human CYP2C9 by Rifampicin, Hyperforin, and Phenobarbital Is Mediated by the Pregnane X Receptor
TLDR
This is the first report to demonstrate that the nuclear receptor PXR mediates induction of CYP2C9 with rifampicin, phenobarbital, and hyperforin, and the cis-element essential for this response is identified. Expand
...
1
2
3
4
5
...