Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen

Clinical pharmacokinetics and pharmacogenetics of tamoxifen and endoxifen / A.B. Sanchez-Spitman, J.J. Swen, V.O. Dezentje, D.J.A.R Moes, H. Gelderblom, H.J. Guchelaar

  • Expert Review of Clinical Pharmacology 12 (2019) 6 (30 April), p. 523-536
  • PMID: 31008668
  • DOI: 10.1080/17512433.2019.1610390


Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30-100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.

Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.

Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available.

Keywords: Breast cancer; endocrine therapy; endoxifen; pharmacogenetics; pharmacokinetics; tamoxifen; therapeutic drug monitoring.

Original document


Research / Study
30 April 2019
Dezentje, V.O.
Gelderblom, H.
Guchelaar, H.J.
Moes, D.J.A.R.
Sanchez-Spitman, A.B.
Swen, J.J.
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Leids Universitair Medisch Centrum (LUMC) - Leiden University Medical Center
Nederlands Kanker Instituut (NKI) - Netherlands Cancer Institute
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10 January 2022
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18 January 2022
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