循环生物标志物,而不是基因定型,以建立代谢器表型
Roman Tremmel1,2, Ute Hofmann1,2, Mathias Haag1,2
1Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany;
Annual review of pharmacology and toxicology
|August 16, 2023
概括
药物基因组学 (PGx) 可以个性化医药,但仅仅基因数据具有有限的预测能力. 包括液体活检和人工智能在内的表型化策略可以更好地预测药物反应,并减少药物不良反应.
科学领域:
- 药物基因组学 药物基因组学
- 药物新陈代谢 药物新陈代谢
- 个性化医疗是个性化的医疗.
背景情况:
- 药物基因组学 (PGx) 旨在通过预测患者反应和预防药物不良反应来个性化药物治疗.
- 目前的PGx主要使用ADME标 (酶,载体) 的遗传信息来预测表型,但表型-基因型一致性往往是有限的.
研究的目的:
- 审查目前超越遗传学的表型化策略,用于预测药物反应.
- 突出个人化医学中微创方法和先进建模的潜力.
主要方法:
- 讨论使用外源异生生物或内源化合物的表型化策略.
- 探索最少侵入性的液体活检方法,特别是外体组分析.
- 医药计量建模和人工智能的整合,用于增强表型预测.
主要成果:
- 现型-基因型对应性有限,需要使用替代预测方法.
- 最少侵入性表型,特别是使用肝脏衍生的外体,显示出对评估代谢和运输能力的希望.
- 药量计模型和人工智能可以显著提高表型预测的准确性.
结论:
- 个性化治疗策略应该包括超越遗传学的表型化,以获得更大的临床效用.
- 需要进一步的前性研究来验证以表型为指导的个性化药物的临床有效性.
- 基于外体的ADME表型化和AI集成代表了精密药物治疗的有希望的进步.
相关概念视频
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess the...
Pharmacogenetics and Pharmacogenomics: Overview
Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...


