Pharmacodynamic Drug-Drug Interactions
Pharmacodynamic Drug-Drug Interactions
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DOI：
10.1002/cpt.1434
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发表时间：
2019-06-01
影响因子：
6.7
通讯作者：
Mager, Donald E.
中科院分区：
文献类型：
--
作者：
Niu, Jin;Straubinger, Robert M.;Mager, Donald E.
当一种药物的药理学作用被联合方案中的另一种药物的药理学作用改变时，发生药效学药物-药物相互作用（DDI）。DDI通常被分类为协同，相加或拮抗性质，尽管这些术语经常被误用。在一个复杂的病理生理系统中，相互作用的机制可能发生在相同的靶点或通过替代途径。需要采用建模和模拟方法定量评价药效学DDI，以确定和优化安全有效的联合治疗方案。本文综述了药物动力学DDI研究中的机遇和挑战，并重点介绍了评价药物动力学DDI的定量方法，特别强调在DDI研究中使用基于机制的建模和模拟。实验和计算技术的进步将使药效学DDI在药物发现、开发和治疗中的应用更好、模型知情的评估成为可能。
Pharmacodynamic drug-drug interactions (DDIs) occur when the pharmacological effect of one drug is altered by that of another drug in a combination regimen. DDIs often are classified as synergistic, additive, or antagonistic in nature, albeit these terms are frequently misused. Within a complex pathophysiological system, the mechanism of interaction may occur at the same target or through alternate pathways. Quantitative evaluation of pharmacodynamic DDIs by employing modeling and simulation approaches is needed to identify and optimize safe and effective combination therapy regimens. This review investigates the opportunities and challenges in pharmacodynamic DDI studies and highlights examples of quantitative methods for evaluating pharmacodynamic DDIs, with a particular emphasis on the use of mechanism-based modeling and simulation in DDI studies. Advancements in both experimental and computational techniques will enable the application of better, model-informed assessments of pharmacodynamic DDIs in drug discovery, development, and therapeutics.