Israili Z H, Dayton P G
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Drug Metab Rev. 2001 May;33(2):161-235. doi: 10.1081/dmr-100104402.
For about half a century, the binding of drugs to plasma albumin, the "silent receptor," has been recognized as one of the major determinants of drug action, distribution, and disposition. In the last decade, the binding of drugs, especially but not exclusively basic entities, to another plasma protein, alpha 1-acid glycoprotein (AAG), has increasingly become important in this regard. The present review points out that hundreds of drugs with diverse structures bind to this glycoprotein. Although plasma concentration of AAG is much lower than that of albumin, AAG can become the major drug binding macromolecule in plasma with significant clinical implications. Also, briefly reviewed are the physiological, pathological, and genetic factors that influence binding, the role of AAG in drug-drug interactions, especially the displacement of drugs and endogenous substances from AAG binding sites, and pharmacokinetic and clinical consequences of such interactions. It can be predicted that in the future, rapid automatic methods to measure binding to albumin and/or AAG will routinely be used in drug development and in clinical practice to predict and/or guide therapy.
在大约半个世纪的时间里，药物与血浆白蛋白（“沉默受体”）的结合一直被认为是药物作用、分布和处置的主要决定因素之一。在过去十年中，药物尤其是但不限于碱性物质与另一种血浆蛋白α1-酸性糖蛋白（AAG）的结合在这方面变得越来越重要。本综述指出，数百种结构各异的药物与这种糖蛋白结合。尽管AAG的血浆浓度远低于白蛋白，但AAG可成为血浆中主要的药物结合大分子，具有重要的临床意义。此外，还简要回顾了影响结合的生理、病理和遗传因素、AAG在药物相互作用中的作用，特别是药物和内源性物质从AAG结合位点的置换，以及此类相互作用的药代动力学和临床后果。可以预测，未来在药物研发和临床实践中，将常规使用快速自动方法来测量药物与白蛋白和/或AAG的结合，以预测和/或指导治疗。
