Human serum albumin and alpha-1-acid glycoprotein (HSA and AGP)

Human serum albumin (HSA) and alpha-1-acid glycoprotein (AGP) are the two most significant plasma proteins involved in the binding and transport of endogenous and exogenous compounds in the blood (UniProt P02768; UniProt P02763). HSA is the most abundant protein in plasma and primarily binds acidic and neutral drugs at specific sites such as Sudlow's sites I and II (PubMed: 25974265). In contrast, AGP is an acute-phase reactant that primarily binds basic drugs, and its concentration can fluctuate significantly during systemic inflammation (PubMed: 11336342). Together, these proteins play a critical role in determining the "free fraction" of a drug, which is the pharmacologically active portion capable of reaching target tissues and being metabolized or excreted (StatPearls: NBK545240). While they are not traditional therapeutic targets, they are essential considerations in drug development for optimizing pharmacokinetics, predicting drug-drug interactions, and adjusting dosages in specific patient populations (PubMed: 15970133). Changes in the concentrations of these proteins, due to disease states like liver failure or chronic inflammation, can significantly alter the safety and efficacy profiles of highly protein-bound medications (PubMed: 11924856).

Other names

Plasma binding proteinsSerum albuminOrosomucoidORM1ORM2ALBAlpha-1-acid glycoprotein

These proteins do not typically serve as therapeutic targets; instead, they function as pharmacokinetic modulators by binding drugs in the plasma, thereby sequestering them and determining the unbound fraction available for tissue distribution and receptor interaction (PubMed: 15970133).