학술논문
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.
Document Type
Academic Journal
Author
Saghafi F; Department of Clinical Pharmacy, School of Pharmacy, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.; Salehifar E; Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.; Ebrahimi P; Department of Chemistry, Faculty of Sciences, Golestan University, Gorgan, Iran.; Shiran MR; Department of Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.; Zaboli E; Department of Internal Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.; Sohrevardi SM; Department of Clinical Pharmacy, School of Pharmacy, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.; Jamialahmadi T; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.; Sahebnasagh A; Clinical Research Center, Department of Internal Medicine, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran. Electronic address: masoomehsahebnasagh@gmail.com.; Sahebkar A; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Source
Publisher: Elsevier Science Country of Publication: England NLM ID: 8309336 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-264X (Electronic) Linking ISSN: 07317085 NLM ISO Abbreviation: J Pharm Biomed Anal Subsets: MEDLINE
Subject
Language
English
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.
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.
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.
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.
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.
(Copyright © 2023. Published by Elsevier B.V.)
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.
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.
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.
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.
(Copyright © 2023. Published by Elsevier B.V.)