Serum albumin and other endogenous plasma carrier proteins (HSA/AGP)

Serum albumin and other endogenous plasma carrier proteins, such as alpha-1-acid glycoprotein (AGP) and transthyretin, are essential components of the circulatory system responsible for the transport and distribution of various substances (StatPearls, 2023). Serum albumin is the most prevalent, providing the majority of plasma oncotic pressure and binding a diverse array of ligands including fatty acids, bile salts, and bilirubin (UniProt, P02768). These proteins significantly influence the pharmacokinetics of drugs; albumin typically binds acidic and neutral drugs, while AGP binds basic drugs (PubMed, PMID: 25707815). The binding affinity between a drug and these carriers determines the "free fraction," which is the portion of the drug available to exert a therapeutic effect or undergo metabolism and excretion (NIH, 2022). In clinical settings, alterations in the levels of these proteins—due to liver disease, kidney dysfunction, or systemic inflammation—can lead to significant changes in drug efficacy and toxicity (PubMed, PMID: 30165378). Additionally, albumin is used therapeutically for fluid resuscitation and as a scaffold for long-acting drug formulations to extend plasma half-life (PubChem, CID: 16132360).

Other names

Human serum albuminAlpha-1-acid glycoproteinTransthyretinSex hormone-binding globulinCorticosteroid-binding globulinLipoproteinsOrosomucoidPrealbuminPlasma carrier proteins

Drugs bind reversibly to specific hydrophobic pockets on these proteins, such as Sudlow's sites I and II on albumin, which serves to solubilize lipophilic compounds, regulate the concentration of free (active) drug in the plasma, and provide a circulating reservoir that extends the biological half-life of the therapeutic agent (PubMed, PMID: 25707815).