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  • Title: Effect of alpha-1-acid glycoprotein binding on pharmacokinetics and pharmacodynamics.
    Author: Huang Z, Ung T.
    Journal: Curr Drug Metab; 2013 Feb; 14(2):226-38. PubMed ID: 23092311.
    Abstract:
    Alpha-1-acid glycoprotein (AGP, also known as AAG or orosomucoid) is an important plasma protein involved in the binding and transport of many drugs, especially basic compounds. AGP has some unique drug-binding properties that differ from those of albumin. For example, the plasma concentration of AGP is relatively low and there is only one drug-binding site in each AGP molecule. Thus, binding to AGP is saturable and displaceable. This could have potential implications for drug-drug interactions or toxicological consequences. Furthermore, AGP is an acute phase protein and the concentration of AGP in plasma can significantly increase in various diseases (such as cancer and inflammatory diseases) or following trauma (burns, surgery). Changes in AGP concentration could potentially alter the free fraction of drugs in plasma or at their target sites and eventually affect their pharmacokinetic disposition and pharmacological action. Given that an increasing number of drugs have been shown to bind preferrentially to AGP, a better understanding of this unique interaction may provide great benefit for drug discovery and development. In this review, we will focus on the effect of altered AGP binding on the pharmacokinetics and pharmacodynamics (PK/PD) of drugs, as well as the species differences in AGP binding.
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