临床药物遗传学实施联盟（CPIC）关于 CYP2D6 和他莫昔芬治疗的指南。
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and Tamoxifen Therapy.
机构信息
Department of Oncology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota, USA.
Department of Biomedical Data Science, Stanford University, Stanford, California, USA.
出版信息
Clin Pharmacol Ther. 2018 May;103(5):770-777. doi: 10.1002/cpt.1007. Epub 2018 Jan 31.
Abstract
Tamoxifen is biotransformed by CYP2D6 to 4-hydroxytamoxifen and 4-hydroxy N-desmethyl tamoxifen (endoxifen), both with greater antiestrogenic potency than the parent drug. Patients with certain CYP2D6 genetic polymorphisms and patients who receive strong CYP2D6 inhibitors exhibit lower endoxifen concentrations and a higher risk of disease recurrence in some studies of tamoxifen adjuvant therapy of early breast cancer. We summarize evidence from the literature and provide therapeutic recommendations for tamoxifen based on CYP2D6 genotype.
摘要
他莫昔芬经 CYP2D6 生物转化为 4-羟基他莫昔芬和 4-羟基 N-去甲基他莫昔芬（依西美坦），这两种代谢物均比母体药物具有更强的抗雌激素作用。在早期乳腺癌他莫昔芬辅助治疗的一些研究中，具有某些 CYP2D6 遗传多态性的患者和接受强 CYP2D6 抑制剂的患者表现出较低的依西美坦浓度和更高的疾病复发风险。我们总结了文献中的证据，并根据 CYP2D6 基因型为他莫昔芬提供了治疗建议。
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本文引用的文献
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Improved Prediction of Endoxifen Metabolism by CYP2D6 Genotype in Breast Cancer Patients Treated with Tamoxifen.通过CYP2D6基因型改善对接受他莫昔芬治疗的乳腺癌患者中内昔芬代谢的预测
Front Pharmacol. 2017 Aug 24;8:582. doi: 10.3389/fphar.2017.00582. eCollection 2017.
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Effect of CYP3A4*22, CYP3A5*3, and CYP3A combined genotypes on tamoxifen metabolism.细胞色素P450 3A4*22、细胞色素P450 3A5*3及细胞色素P450 3A联合基因型对他莫昔芬代谢的影响。
Eur J Clin Pharmacol. 2017 Dec;73(12):1589-1598. doi: 10.1007/s00228-017-2323-2. Epub 2017 Aug 28.
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CYP2C19*2 and CYP2C19*17 variants and effect of tamoxifen on breast cancer recurrence: Analysis of the International Tamoxifen Pharmacogenomics Consortium dataset.CYP2C19*2 和 CYP2C19*17 变体与他莫昔芬对乳腺癌复发的影响：国际他莫昔芬药物基因组学联盟数据集的分析。
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Significant Effect of Polymorphisms in on Response to Tamoxifen Therapy for Breast Cancer: A Prospective Multicenter Study.在乳腺癌对他莫昔芬治疗的反应中，的多态性有显著影响：一项前瞻性多中心研究。
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