Human serum albumin and other plasma proteins (HSA)

Human serum albumin (HSA) and other plasma proteins, including alpha-1-acid glycoprotein (AAG) and lipoproteins, are the primary protein constituents of blood plasma that facilitate the transport of endogenous and exogenous molecules. HSA is the most prevalent protein in the blood and is essential for maintaining oncotic pressure and buffering pH, while also serving as a major carrier for acidic and neutral drugs (StatPearls, 2023) [1]. AAG, an acute-phase reactant, primarily binds basic drugs and its levels can fluctuate significantly during inflammation (NCBI, 2022) [2]. These proteins are critical determinants of drug pharmacokinetics, as the degree of protein binding dictates the free fraction of a drug available for therapeutic action and elimination (Merck Manual, 2023) [3]. While not typically modulated as therapeutic targets to treat disease, they are vital in drug development for predicting distribution, half-life, and potential drug-drug interactions (PubMed, 2021) [4]. Alterations in the concentrations of these proteins due to liver or kidney dysfunction can lead to significant changes in drug efficacy and toxicity profiles (UniProt, 2024) [5].

Other names

AlbuminALBSerum albuminAlpha-1-acid glycoproteinAAGPlasma carrier proteinsLipoproteinsSerum proteins

Plasma proteins act as a reversible reservoir for drugs; binding occurs at specific hydrophobic pockets (e.g., Sudlow's sites I and II on albumin), which sequesters the drug in the plasma, reduces the volume of distribution, and protects the drug from rapid metabolism and excretion, thereby regulating the concentration of the pharmacologically active free fraction.