Chemistry Department, University of Nebraska, 704 Hamilton Hall, Lincoln, NE 68588-0304, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Mar 1;878(7-8):705-8. doi: 10.1016/j.jchromb.2010.01.016. Epub 2010 Jan 25.
High-performance affinity chromatography was used to study binding by the drug lidocaine to human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP). AGP had strong binding to lidocaine, with an association equilibrium constant (K(a)) of 1.1-1.7 x 10(5) M(-1) at 37 degrees C and pH 7.4. Lidocaine had weak to moderate binding to HSA, with a K(a) in the range of 10(3) to 10(4) M(-1). Competitive experiments with site selective probes showed that lidocaine was interacting with Sudlow site II of HSA and the propranolol site of AGP. These results agree with previous observations in the literature and provide a better quantitative understanding of how lidocaine binds to these serum proteins and is transported in the circulation. This study also demonstrates how HPAC can be used to examine the binding of a drug with multiple serum proteins and provide detailed information on the interaction sites and equilibrium constants that are involved in such processes.
高效亲和色谱法用于研究药物利多卡因与人血清白蛋白（HSA）和α(1)-酸性糖蛋白（AGP）的结合。AGP 与利多卡因具有很强的结合能力，在 37°C 和 pH 7.4 时的缔合平衡常数（K(a)）为 1.1-1.7×10(5)M(-1)。利多卡因与 HSA 的结合能力较弱到中等，K(a)在 10(3)到 10(4)M(-1)范围内。与位点选择性探针的竞争实验表明，利多卡因与 HSA 的 Sudlow 位点 II 和 AGP 的普萘洛尔位点相互作用。这些结果与文献中的先前观察结果一致，并提供了对利多卡因与这些血清蛋白结合以及在循环中运输的更好的定量理解。本研究还展示了 HPAC 如何用于检查具有多种血清蛋白的药物的结合，并提供有关涉及此类过程的相互作用位点和平衡常数的详细信息。
