Identification of non-adherence to adjuvant letrozole using a population pharmacokinetics approach in hormone receptor-positive breast cancer patients.
CYP2A6
CYP3A4/5
adherence
letrozole
non-linear mixed-effects modelling
pharmacokinetics
Journal
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
ISSN: 1879-0720
Titre abrégé: Eur J Pharm Sci
Pays: Netherlands
ID NLM: 9317982
Informations de publication
Date de publication:
22 May 2024
22 May 2024
Historique:
received:
27
11
2023
revised:
05
04
2024
accepted:
21
05
2024
medline:
25
5
2024
pubmed:
25
5
2024
entrez:
24
5
2024
Statut:
aheadofprint
Résumé
Letrozole, an aromatase inhibitor metabolised via CYP2A6 and CYP3A4/5 enzymes, is used as adjuvant therapy for women with hormone receptor (HR)-positive early breast cancer. The objective of this study was to quantify the impact of CYP2A6 genotype on letrozole pharmacokinetics (PK), to identify non-adherent patients using a population approach and explore the possibility of a relationship between non-adherence and early relapse. Breast cancer patients enrolled in the prospective PHACS study (ClinicalTrials.gov NCT01127295) and treated with adjuvant letrozole 2.5 mg/day were included. Trough letrozole concentrations (C 617 patients contributing 2534 plasma concentrations were included and led to a one-compartment PK model with linear absorption and elimination. Model-based methods identified 28% of patients as non-adherent based on high fluctuations of their C These findings will help future investigations focusing on the exposure-efficacy relationship for letrozole in adjuvant setting.
Sections du résumé
BACKGROUND
BACKGROUND
Letrozole, an aromatase inhibitor metabolised via CYP2A6 and CYP3A4/5 enzymes, is used as adjuvant therapy for women with hormone receptor (HR)-positive early breast cancer. The objective of this study was to quantify the impact of CYP2A6 genotype on letrozole pharmacokinetics (PK), to identify non-adherent patients using a population approach and explore the possibility of a relationship between non-adherence and early relapse.
METHODS
METHODS
Breast cancer patients enrolled in the prospective PHACS study (ClinicalTrials.gov NCT01127295) and treated with adjuvant letrozole 2.5 mg/day were included. Trough letrozole concentrations (C
RESULTS
RESULTS
617 patients contributing 2534 plasma concentrations were included and led to a one-compartment PK model with linear absorption and elimination. Model-based methods identified 28% of patients as non-adherent based on high fluctuations of their C
CONCLUSIONS
CONCLUSIONS
These findings will help future investigations focusing on the exposure-efficacy relationship for letrozole in adjuvant setting.
Identifiants
pubmed: 38788907
pii: S0928-0987(24)00121-0
doi: 10.1016/j.ejps.2024.106809
pii:
doi:
Banques de données
ClinicalTrials.gov
['NCT01127295']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
106809Informations de copyright
Copyright © 2024. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no competing interests to declare that are relevant to the content of this article.