Rapid characterization of drug-drug interaction in plasma protein binding using a surface plasmon resonance biosensor
Rapid characterization of drug-drug interaction in plasma protein binding using a surface plasmon resonance biosensor
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DOI：
10.2133/dmpk.23.120
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发表时间：
2008-01-01
影响因子：
2.1
通讯作者：
Yamaoka, Takashi
中科院分区：
文献类型：
--
作者：
Kuroda, Yukihiro;Saito, Madoka;Yamaoka, Takashi
利用表面等离子体共振(SPR)生物传感器对血浆蛋白结合中药物与药物相互作用的高通量特征进行了研究。本研究使用的方法能够区分结合抑制、直接竞争和负变构效应两种模式，这在传统的SPR方法中是困难的。用两个理论方程表示直接竞争结合和独立结合的SPR结合反应。用非线性最小二乘回归方程处理人血清白蛋白的实验结合数据。通过这种方法，药物与药物的相互作用分为直接竞争、独立结合和变构相互作用三种模式，这与以前的报道基本一致。此外，还粗略估计了直接竞争和独立结合的离解常数。分析吞吐量几乎与以前的报告一样高；每次注射三分钟。这种方法是在新药开发的早期阶段表征药物-药物相互作用的有力工具。
High-throughput characterization of drug-drug interactions in plasma protein binding was demonstrated by using a surface plasmon resonance (SPR) biosensor. The method used in this study enabled the discrimination between the two modes of binding inhibition, direct competition and negative allosteric effect, which was difficult in conventional SPR approaches. Two theoretical equations were used representing SPR binding response for directly competitive binding or for independent binding. The experimental binding data for human serum albumin was processed by non-linear least squared regression of the equations. By this approach, drug-drug interactions were classified into three modes, direct competition, independent binding, and allosteric interaction, which were almost consistent with previous reports. In addition, dissociation constants were also estimated roughly for direct competition and for independent binding. The analytical throughput was almost as high as in the previous reports; three minutes per injection. This method is a powerful tool for the characterization of drug-drug interaction at an early stage of new drug development.