Clinical Pharmacokinetics

, Volume 46, Issue 2, pp 133–157 | Cite as

Pharmacokinetic Drug Interactions Involving 17α-Ethinylestradiol

A New Look at an Old Drug
  • Hongjian Zhang
  • Donghui Cui
  • Bonnie Wang
  • Yong-Hae Han
  • Praveen Balimane
  • Zheng Yang
  • Michael Sinz
  • A. David Rodrigues
Review Article


17α-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 [rifampin]) can lead to breakthrough bleeding and contraceptive failure. Conversely, inhibitors of drug-metabolising enzymes can give rise to elevated EE plasma concentrations and increased risks of vascular disease and hypertension. In vitro studies have also shown that EE inhibits a number of human CYP enzymes, such as CYP2C19, CYP3A4 and CYP2B6. Consequently, there are numerous reports in the literature describing EE-containing OC formulations as perpetrators of pharmacokinetic drug interactions. Because EE may participate in multiple pharmacokinetic drug interactions as either a victim or perpetrator, pharmaceutical companies routinely conduct clinical drug interaction studies with EE-containing OCs when evaluating new chemical entities in development. It is therefore critical to understand the mechanisms underlying these drug interactions. Such an understanding can enable the interpretation of clinical data and lead to a greater appreciation of the profile of the drug by physicians, clinicians and regulators. This article summarises what is known of the drug-metabolising enzymes and transporters governing the metabolism, disposition and excretion of EE. An effort is made to relate this information to known clinical drug-drug interactions. The inhibition and induction of drug-metabolising enzymes by EE is also reviewed.


Progestin Selegiline Human Liver Microsome Breast Cancer Resistance Protein Pharmacokinetic Drug Interaction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



All authors are employees of Bristol-Myers Squibb USA. The authors have no conflicts of interest that are directly relevant to the content of this review.


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Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Hongjian Zhang
    • 1
  • Donghui Cui
    • 2
  • Bonnie Wang
    • 1
  • Yong-Hae Han
    • 1
  • Praveen Balimane
    • 1
  • Zheng Yang
    • 1
  • Michael Sinz
    • 3
  • A. David Rodrigues
    • 1
  1. 1.Metabolism and Pharmacokinetics, Pharmaceutical Candidate OptimizationBristol-Myers Squibb Pharmaceutical Research InstitutePrincetonUSA
  2. 2.Biotransformation, Pharmaceutical Candidate OptimizationBristol-Myers Squibb Pharmaceutical Research InstitutePrincetonUSA
  3. 3.Metabolism and PharmacokineticsBristol-Myers Squibb Pharmaceutical Research InstituteWalingfordUSA

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