Factors Influencing Pharmacokinetics of Tamoxifen in Breast Cancer Patients: A Systematic Review of Population Pharmacokinetic Models.

breast cancer population pharmacokinetics systematic review tamoxifen

Journal

Biology
ISSN: 2079-7737
Titre abrégé: Biology (Basel)
Pays: Switzerland
ID NLM: 101587988

Informations de publication

Date de publication:
28 Dec 2022
Historique:
received: 23 11 2022
revised: 21 12 2022
accepted: 25 12 2022
entrez: 21 1 2023
pubmed: 22 1 2023
medline: 22 1 2023
Statut: epublish

Résumé

Tamoxifen is useful in managing breast cancer and it is reported to have significant variability in its pharmacokinetics. This review aimed to summarize reported population pharmacokinetics studies of tamoxifen and to identify the factors affecting the pharmacokinetics of tamoxifen in adult breast cancer patients. A systematic search was undertaken in Scopus, Web of Science, and PubMed for papers published in the English language from inception to 20 August 2022. Studies were included in the review if the population pharmacokinetic modeling was based on non-linear mixed-effects modeling with a parametric approach for tamoxifen in breast cancer patients. After initial selection, 671 records were taken for screening. A total of five studies were selected from Scopus, Web of Science, PubMed, and by manual searching. The majority of the studies were two-compartment models with first-order absorption and elimination to describe tamoxifen and its metabolites' disposition. The CYP2D6 phenotype and CYP3A4 genotype were the main covariates that affected the metabolism of tamoxifen and its metabolites. Other factors influencing the drug's pharmacokinetics included age, co-medication, BMI, medication adherence, CYP2B6, and CYP2C19 genotype. The disposition of tamoxifen and its metabolites varies primarily due to the CYP2D6 phenotype and CYP3A4 genotype. However, other factors, such as anthropometric characteristics and menopausal status, should also be addressed when accounting for this variability. All these studies should be externally evaluated to assess their applicability in different populations and to use model-informed dosing in the clinical setting.

Sections du résumé

BACKGROUND BACKGROUND
Tamoxifen is useful in managing breast cancer and it is reported to have significant variability in its pharmacokinetics. This review aimed to summarize reported population pharmacokinetics studies of tamoxifen and to identify the factors affecting the pharmacokinetics of tamoxifen in adult breast cancer patients.
METHOD METHODS
A systematic search was undertaken in Scopus, Web of Science, and PubMed for papers published in the English language from inception to 20 August 2022. Studies were included in the review if the population pharmacokinetic modeling was based on non-linear mixed-effects modeling with a parametric approach for tamoxifen in breast cancer patients.
RESULTS RESULTS
After initial selection, 671 records were taken for screening. A total of five studies were selected from Scopus, Web of Science, PubMed, and by manual searching. The majority of the studies were two-compartment models with first-order absorption and elimination to describe tamoxifen and its metabolites' disposition. The CYP2D6 phenotype and CYP3A4 genotype were the main covariates that affected the metabolism of tamoxifen and its metabolites. Other factors influencing the drug's pharmacokinetics included age, co-medication, BMI, medication adherence, CYP2B6, and CYP2C19 genotype.
CONCLUSION CONCLUSIONS
The disposition of tamoxifen and its metabolites varies primarily due to the CYP2D6 phenotype and CYP3A4 genotype. However, other factors, such as anthropometric characteristics and menopausal status, should also be addressed when accounting for this variability. All these studies should be externally evaluated to assess their applicability in different populations and to use model-informed dosing in the clinical setting.

Identifiants

pubmed: 36671744
pii: biology12010051
doi: 10.3390/biology12010051
pmc: PMC9855885
pii:
doi:

Types de publication

Journal Article Review

Langues

eng

Subventions

Organisme : Indian Council of Medical Research
ID : 45/15/2022-PHA/BMS

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Auteurs

Jaya Shree Dilli Batcha (JS)

Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India.

Arun Prasath Raju (AP)

Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India.

Saikumar Matcha (S)

Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India.

Elstin Anbu Raj S (EA)

Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India.
Public Health Evidence South Asia, Department of Health Information, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India.

Karthik S Udupa (KS)

Department of Medical Oncology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India.

Vikram Gota (V)

Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Mumbai 410 210, Maharashtra, India.

Surulivelrajan Mallayasamy (S)

Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India.
Center for Pharmacometrics, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India.

Classifications MeSH