Insights into pharmacogenetics, drug-gene interactions, and drug-drug-gene interactions.

IF 3.4 2区 医学 Q2 PHARMACOLOGY & PHARMACY Drug Metabolism Reviews Pub Date : 2024-08-18 DOI:10.1080/03602532.2024.2385928
Laura E Russell, Katrina G Claw, Kaja M Aagaard, Sarah M Glass, Kuheli Dasgupta, F Leah Nez, Alex Haimbaugh, Benjamin J Maldonato, Jaydeep Yadav
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Abstract

This review explores genetic contributors to drug interactions, known as drug-gene and drug-drug-gene interactions (DGI and DDGI, respectively). This article is part of a mini-review issue led by the International Society for the Study of Xenobiotics (ISSX) New Investigators Group. Pharmacogenetics (PGx) is the study of the impact of genetic variation on pharmacokinetics (PK), pharmacodynamics (PD), and adverse drug reactions. Genetic variation in pharmacogenes, including drug metabolizing enzymes and drug transporters, is common and can increase the risk of adverse drug events or contribute to reduced efficacy. In this review, we summarize clinically actionable genetic variants, and touch on methodologies such as genotyping patient DNA to identify genetic variation in targeted genes, and deep mutational scanning as a high-throughput in vitro approach to study the impact of genetic variation on protein function and/or expression in vitro. We highlight the utility of physiologically based pharmacokinetic (PBPK) models to integrate genetic and chemical inhibitor and inducer data for more accurate human PK simulations. Additionally, we analyze the limitations of historical ethnic descriptors in pharmacogenomics research. Altogether, the work herein underscores the importance of identifying and understanding complex DGI and DDGIs with the intention to provide better treatment outcomes for patients. We also highlight current barriers to wide-scale implementation of PGx-guided dosing as standard or care in clinical settings.

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对药物遗传学、药物-基因相互作用以及药物-药物-基因相互作用的见解。
这篇综述探讨了药物相互作用的遗传因素,即药物-基因和药物-基因相互作用(分别称为 DGI 和 DDGI)。这篇文章是国际外来生物研究学会(ISSX)新研究者小组领导的小型评论刊物的一部分。药物遗传学(PGx)是一门研究基因变异对药物代谢动力学(PK)、药物动力学(PD)和药物不良反应影响的学科。药物基因(包括药物代谢酶和药物转运体)的遗传变异很常见,可增加药物不良反应的风险或导致药效降低。在这篇综述中,我们总结了临床上可操作的基因变异,并介绍了一些方法,如通过对患者 DNA 进行基因分型来确定目标基因中的基因变异,以及将深度突变扫描作为一种高通量体外方法来研究基因变异对体外蛋白质功能和/或表达的影响。我们强调了基于生理学的药代动力学(PBPK)模型在整合基因和化学抑制剂及诱导剂数据以进行更准确的人体 PK 模拟方面的效用。此外,我们还分析了药物基因组学研究中历史种族描述符的局限性。总之,本文的研究工作强调了识别和理解复杂的 DGI 和 DDGI 的重要性,目的是为患者提供更好的治疗效果。我们还强调了目前将 PGx 指导用药作为标准或护理在临床环境中广泛实施的障碍。
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
Drug Metabolism Reviews
Drug Metabolism Reviews 医学-药学
CiteScore
11.10
自引率
1.70%
发文量
21
审稿时长
1 months
期刊介绍: Drug Metabolism Reviews consistently provides critically needed reviews of an impressive array of drug metabolism research-covering established, new, and potential drugs; environmentally toxic chemicals; absorption; metabolism and excretion; and enzymology of all living species. Additionally, the journal offers new hypotheses of interest to diverse groups of medical professionals including pharmacologists, toxicologists, chemists, microbiologists, pharmacokineticists, immunologists, mass spectroscopists, as well as enzymologists working in xenobiotic biotransformation.
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