对药物遗传学,药物基因相互作用和药物药物基因相互作用的洞察
Laura E Russell1, Katrina G Claw2, Kaja M Aagaard2
1Drug Metabolism and Pharmacokinetics, AbbVie Inc, North Chicago, IL, USA.
Drug metabolism reviews
|August 18, 2024
概括
遗传变异影响药物相互作用,影响患者治疗结果. 了解药物 - 基因和药物 - 药物 - 基因相互作用对于个性化医疗和提高药物疗效至关重要.
科学领域:
- 药物遗传学和药物新陈代谢
- 基因组学和个性化医学
背景情况:
- 药物基因 (药物代谢酶,载体) 的遗传变异很常见.
- 这些变化可能导致药物不良事件或降低药物的疗效.
- 药物-基因相互作用 (DGI) 和药物-药物-基因相互作用 (DDGI) 复杂化了治疗.
研究的目的:
- 审查DGI和DDGI的遗传贡献者.
- 总结临床可行的遗传变异及其研究方法.
- 突出实施药物遗传学指导剂量的障碍.
主要方法:
- 关于药物遗传学,DGI和DDGI的文献综述.
- 讨论基因型定型和深度突变扫描用于变种分析.
- 整合基于生理学的药理动力学 (PBPK) 模型与遗传和化学数据.
主要成果:
- 确定了临床可操作的遗传变异及其对药物反应的影响.
- 基因定型和PBPK建模等方法有助于预测药物相互作用.
- 分析了药物基因组学研究中历史种族描述者的局限性.
结论:
- 了解复杂的DGI和DDGI对于改善患者治疗结果至关重要.
- 基于生理学的药理动力学模型提高了模拟人类药理动力学的准确性.
- 药物遗传学指导剂量的广泛临床实施的障碍仍然存在.
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