Alpha-1-acid glycoprotein and Serum albumin (AGP and HSA)

Alpha-1-acid glycoprotein (AGP) and serum albumin are the primary plasma proteins responsible for the reversible binding and systemic transport of a wide variety of endogenous and exogenous compounds. Serum albumin, the most abundant protein in human plasma, is a 66 kDa monomeric protein that maintains vascular oncotic pressure and serves as the principal carrier for long-chain fatty acids, bilirubin, and acidic or neutral drugs [UniProt P02768]. It contains two primary binding sites, known as Sudlow's sites I and II, which accommodate drugs like warfarin and ibuprofen [StatPearls, NBK459132]. In contrast, AGP is a 41-43 kDa heavily glycosylated acute-phase protein that primarily binds basic and lipophilic drugs, such as propranolol and lidocaine [PubMed, 12452544]. AGP levels can increase significantly during inflammation, infection, or malignancy, leading to decreased free drug fractions and potentially reduced therapeutic efficacy [UniProt P02763]. Because only the unbound (free) fraction of a drug is pharmacologically active and capable of crossing biological membranes, the concentration and binding capacity of these proteins are critical determinants of drug pharmacokinetics and pharmacodynamics. Consequently, clinical conditions that alter the levels of these proteins, such as liver cirrhosis or acute inflammatory states, necessitate careful dosage adjustments for drugs with high plasma protein binding [PubMed, 21473620].

Other names

OrosomucoidORM1ORM2Human Serum AlbuminALBPlasma protein binding proteins

These proteins act as systemic carriers that sequester drugs in the intravascular compartment, thereby regulating the free fraction of the drug available for tissue distribution and pharmacological action [PubMed, 21473620].