• Home
  1. Home
  2. Tamoxifen pharmacokinetics and pharmacogenetics in endocrine sensitive breast cancer patients
Doctoral thesis
OA Policy
English

Tamoxifen pharmacokinetics and pharmacogenetics in endocrine sensitive breast cancer patients

Contributors

Dahmane, Elyes Ben Ali

Directors

Csajka, Chantal; Decosterd, Laurent

Defense date

2013-11-26

Abstract

Tamoxifen is used for the treatment of estrogen-sensitive breast cancer. It is a prodrug that is bioactivated into endoxifen, the active metabolite mostly responsible for tamoxifen efficacy. Endoxifen levels show large inter-individual variability. Cytochrome (CYP)2D6 activity was presumed to play a role in predicting this variability and treatment efficacy. The objectives of the thesis were to assess the influence of pharmacogenetic and non-genetic factors on this variability and study the tamoxifen/endoxifen dose-concentration relationship. Based on a population pharmacokinetic study, we confirmed that CYP2D6 phenotype and inhibitors were major factors affecting endoxifen levels. We demonstrated the effectiveness of doubling tamoxifen dose in correcting low endoxifen levels, except for CYP2D6 poor metabolizers or patients under potent CYP2D6 inhibitors. We showed that CYP2D6 phenotype is a modest predictor of endoxifen exposure and demonstrated the rational of endoxifen concentration monitoring for detecting patients at risk of suboptimal treatment and for guiding tamoxifen dosage optimization.

Keywords

  • Population pharmacokinetics
  • Pharmacogenetics
  • Tamoxifen
  • Endoxifen
  • 4-hydroxy-tamoxifen
  • N-desmethyl-tamoxifen
  • Liquid chromatography
  • Mass spectrometry

UNIGE affiliation entities

Citation (ISO format)

DAHMANE, Elyes Ben Ali. Tamoxifen pharmacokinetics and pharmacogenetics in endocrine sensitive breast cancer patients. Doctoral Thesis, 2013. doi: 10.13097/archive-ouverte/unige:33429

Main files (1)

Thesis

Identifiers

1708views
1569downloads

Technical informations

Creation

17/01/2014 11:26:00

First validation

17/01/2014 11:26:00

Update

03/12/2024 08:31:52

Status update

03/12/2024 08:31:52

Last indexation

13/05/2025 16:30:49
All rights reserved by Archive ouverte UNIGE and the University of Geneva
OpenAIRE Indexed & Validated