Endoxifen, a new cornerstone of breast cancer therapy: demonstration of safety, tolerability, and systemic bioavailability in healthy human subjects

Clin Pharmacol Ther. 2010 Dec;88(6):814-7. doi: 10.1038/clpt.2010.196. Epub 2010 Oct 27.


Endoxifen is an active metabolite of tamoxifen, a drug used in the treatment of breast cancer. In order to be clinically effective, tamoxifen must be converted to endoxifen by cytochrome P450 2D6 (CYP2D6). A study involving single escalating oral doses was conducted in humans to evaluate the safety, tolerability, and pharmacokinetics (PK) of endoxifen. This is the first study demonstrating that single oral doses of endoxifen are safe and well tolerated and have sufficient bioavailability to reach systemically effective levels in human subjects. Furthermore, it was found that endoxifen is rapidly absorbed and systemically available and that it displays dose proportionality in peak drug concentrations in plasma (C(max)) and area under the concentration-time curve extrapolated from 0 to ∞ (AUC(0-∞)) over the dose range 0.5-4.0 mg.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Biological Availability
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism*
  • Cytochrome P-450 CYP2D6 / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Tamoxifen / adverse effects
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / metabolism
  • Tamoxifen / pharmacokinetics
  • Tamoxifen / therapeutic use


  • Tamoxifen
  • 4-hydroxy-N-desmethyltamoxifen
  • Cytochrome P-450 CYP2D6