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

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacogenomics 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

Abstract

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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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。

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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics 医学-药学

CiteScore

3.40

自引率

9.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.