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Evaluation of the effect of CYP2D6*3, *4,*10, and *17 polymorphisms on the pharmacokinetic of tamoxifen and its metabolites in patients with hormone-positive breast cancer.
- Source :
-
Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2024 Jan 20; Vol. 238, pp. 115839. Date of Electronic Publication: 2023 Nov 02. - Publication Year :
- 2024
-
Abstract
- Background and Objective: A high rate of interindividual variability in response to tamoxifen (TAM) in breast cancer patients with CYP2D6 polymorphism has been reported, which affects the patient's therapeutic outcome. The objective of this study was to investigate the pharmacogenomics of CYP2D6 genotyping in Iranian patients with breast cancer treated with adjuvant TAM.<br />Methods: A peripheral blood sample was obtained to determine the steady-state plasma concentrations of TAM and its metabolites (Endoxifen (EN) and 4-Hydroxytamoxifen (4-OHT)) using high-performance liquid chromatography with fluorescence detection (HPLC-FLU) assay. We detected CYP2D6 * 3, * 4, * 10, and * 17 single nucleotide polymorphisms via polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method.<br />Results: A total of 84 Iranian estrogen receptor‑positive breast cancer patients receiving the daily dose of 20 mg tamoxifen were recruited. Although a consequent decrease in the median EN and 4-OHT concentrations was observed by comparing poor or intermediate metabolizer patients with an extensive metabolizer population, this difference did not reach a significant level. The mean plasma EN concentrations in poor and intermediate metabolizers were 46.1% (95% CI, 7.4-27.8%) and 59.4% (95% CI, 11.9-37.3%) of extensive metabolizer subjects, respectively. Poor and intermediate metabolizers had the mean plasma 4-OHT concentrations that were 46.6% (95% CI, 0.9-61.7%) and 73.2% (95% CI, 2.7-93.1%) of those of subjects who were extensive metabolizer, respectively.<br />Conclusions: The possible role of genotyping in Iranian patients' response to treatment may explain inter-individual differences in the plasma concentrations of active metabolites of TAM.<br />Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Amirhossein sahebkar reports financial support was provided by Mazandaran University of Medical Sciences. The authors wish to thank the staff and the patients of Tooba clinic, Mazandaran, Sari, Iran.<br /> (Copyright © 2023. Published by Elsevier B.V.)
- Subjects :
- Humans
Female
Cytochrome P-450 CYP2D6 genetics
Cytochrome P-450 CYP2D6 metabolism
Iran
Antineoplastic Agents, Hormonal therapeutic use
Antineoplastic Agents, Hormonal metabolism
Tamoxifen therapeutic use
Tamoxifen metabolism
Polymorphism, Single Nucleotide
Hormones
Genotype
Breast Neoplasms drug therapy
Breast Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-264X
- Volume :
- 238
- Database :
- MEDLINE
- Journal :
- Journal of pharmaceutical and biomedical analysis
- Publication Type :
- Academic Journal
- Accession number :
- 37976989
- Full Text :
- https://doi.org/10.1016/j.jpba.2023.115839