Ten Years' Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics.

Ten Years' Experience with the CYP2D6 Activity Score: A Perspective on Future Investigations to Improve Clinical Predictions for Precision Therapeutics.
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DOI:
10.3390/jpm8020015
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发表时间:
2018-04-17
影响因子:
--
通讯作者:
Leeder JS
Leeder JS
中科院分区:
医学4区
文献类型:
--
作者:
Gaedigk A;Dinh JC;Jeong H;Prasad B;Leeder JS

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关于 CYP2D6 活性评分 (AS) 的开创性论文于十年前首次发表,自 2008 年提出以来,已在药物遗传学领域得到广泛接受。该评分系统有助于将高度复杂的 CYP2D6 双倍型数据转化为患者的表型,以指导药物治疗,并且是临床药物遗传学实施联盟 (CPIC) 发布的所有 CYP2D6 基因/药物对指南的核心。然而,AS 仅解释了在个人和种族之间观察到的部分变异性。在这篇综述中,我们概述了除 CYP2D6 基因型之外导致 CYP2D6 介导的药物代谢变异性的来源,并讨论了可能导致观察到的 CYP2D6 酶活性变异性的其他因素(遗传和非遗传因素)。
The seminal paper on the CYP2D6 Activity Score (AS) was first published ten years ago and, since its introduction in 2008, it has been widely accepted in the field of pharmacogenetics. This scoring system facilitates the translation of highly complex CYP2D6 diplotype data into a patient’s phenotype to guide drug therapy and is at the core of all CYP2D6 gene/drug pair guidelines issued by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The AS, however, only explains a portion of the variability observed among individuals and ethnicities. In this review, we provide an overview of sources in addition to CYP2D6 genotype that contribute to the variability in CYP2D6-mediated drug metabolism and discuss other factors, genetic and non-genetic, that likely contribute to the observed variability in CYP2D6 enzymatic activity.
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发表时间: 1996-10-11
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