Global analytical strategy to measure drug-plasma protein interactions: from high-throughput to in-depth analysis.
Global analytical strategy to measure drug-plasma protein interactions: from high-throughput to in-depth analysis.
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DOI：
10.1016/j.drudis.2013.04.006
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发表时间：
2013-11
影响因子：
7.4
通讯作者：
Karine Vuignier;J. Veuthey;P. Carrupt;Julie Schappler
中科院分区：
文献类型：
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作者：
Karine Vuignier;J. Veuthey;P. Carrupt;Julie Schappler
本文提出了一种创新的、完整的方法学，用于简单地表征药物与血浆蛋白的结合。中等和强蛋白结合剂。第二步涉及更多的-强相互作用的深度表征。选择具有改善的药代动力学的候选药物对于降低药物开发期间的损耗率至关重要，并且是最大的挑战之一面对制药业。血浆蛋白结合率（PPB）是一个重要的参数，对体内药物性能具有重要意义。如今，在制药界最广泛使用的PPB测量技术是平衡透析（艾德）和超滤（UF）。然而，这些技术有一些局限性。因此，我们强调一种替代策略，基于一种全球性的，新的和易于遵循的方法，使用正交技术（即液相色谱法（LC），毛细管电泳（CE），表面等离子体共振（SPR）的生物传感器）来筛选和执行PPB的测定。我们预计，通过这一策略获得的更多知识将导致改进的候选药物。
HighlightsAn innovative and complete methodology is proposed for easy characterization of drug–plasma protein binding.A first screening step is recommended to classify compounds into weak, medium and strong protein binders.The second step involves the more in-depth characterization of strong interactions.The selection of drug candidates with improved pharmacokinetics is essential to reduce the attrition rates during drug development and represents one of the big challenges faced by the pharmaceutical industry. Plasma protein binding (PPB) is an important parameter with significant implications for in vivo drug performance. Today, the most widely used techniques for PPB measurement in the pharmaceutical community are equilibrium dialysis (ED) and ultrafiltration (UF). However, these techniques have some limitations. Thus, we emphasize an alternative strategy, based on a global, new and easy-to-follow methodology, to screen and perform determination of PPB, using orthogonal techniques (ie liquid chromatography (LC), capillary electrophoresis (CE), surface plasmon resonance (SPR) based biosensor). We anticipate that the increased knowledge gained through this strategy will lead to improved drug candidates.