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

Autor:	Dilli Batcha JS; Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India., Raju AP; Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India., Matcha S; Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India., 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., Udupa KS; Department of Medical Oncology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India., Gota V; Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Mumbai 410 210, Maharashtra, India., 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.
Jazyk:	angličtina
Zdroj:	Biology [Biology (Basel)] 2022 Dec 28; Vol. 12 (1). Date of Electronic Publication: 2022 Dec 28.
DOI:	10.3390/biology12010051
Abstrakt:	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: 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: 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: 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.
Databáze:	MEDLINE
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