CYP3A4和CYP2C9基因型对SWOG S0226中系统阿那曲唑和富维司琼浓度的影响。

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2023-08-01 Epub Date: 2023-08-24 DOI:10.2217/pgs-2023-0097

Delaney V Rutherford, Sarah Medley, Nicholas C Henderson, Christina L Gersch, Ted A Vandenberg, Kathy S Albain, Shaker R Dakhil, Nagendra R Tirumali, Julie R Gralow, Gabriel N Hortobagyi, Lajos Pusztai, Rita S Mehta, Daniel F Hayes, Kelley M Kidwell, N Lynn Henry, William E Barlow, James M Rae, Daniel L Hertz

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引用次数: 0

摘要

目的与方法：本研究在SWOG S0226试验参与者中测试了CYP3A4、其他药物基因、SLC28A7（rs11648166）和ALPPL2（rs28845026）的基因型预测活性与内分泌疗法阿那曲唑和富维司琼的全身浓度的相关性。结果：CYP3A4活性低的仅阿曲唑组（即CYP3A4*22携带者）的参与者的全身阿曲唑浓度高于CYP3A4活力高的患者（β-系数=10.03；95%CI:1.42，18.6；p=0.025）。在一项探索性分析中，具有低CYP2C9活性的参与者具有比具有高CYP2C9活动的参与者更低的阿那曲唑浓度和更高的富维司琼浓度。结论：CYP3A4和CYP2C9的遗传变异可能影响内分泌治疗的浓度，并可能有助于个性化给药和改善治疗结果。

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Effects of CYP3A4 and CYP2C9 genotype on systemic anastrozole and fulvestrant concentrations in SWOG S0226.

Objective & methods: This study tested associations of genotype-predicted activity of CYP3A4, other pharmacogenes, SLC28A7 (rs11648166) and ALPPL2 (rs28845026) with systemic concentrations of the endocrine therapies anastrozole and fulvestrant in SWOG S0226 trial participants. Results: Participants in the anastrozole-only arm with low CYP3A4 activity (i.e. CYP3A4*22 carriers) had higher systemic anastrozole concentrations than patients with high CYP3A4 activity (β-coefficient = 10.03; 95% CI: 1.42, 18.6; p = 0.025). In an exploratory analysis, participants with low CYP2C9 activity had lower anastrozole concentrations and higher fulvestrant concentrations than participants with high CYP2C9 activity. Conclusion: Inherited genetic variation in CYP3A4 and CYP2C9 may affect concentrations of endocrine therapy and may be useful to personalize dosing and improve treatment outcomes.

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.