Alpha-1-acid glycoprotein (AGP) (AGP)

Alpha-1-acid glycoprotein (AGP), historically and descriptively referred to as the alkaloid-binding globulin, is a major plasma glycoprotein and a member of the lipocalin family. It is primarily synthesized in the liver and functions as an acute-phase reactant, with its concentration increasing significantly (up to fourfold) in response to systemic inflammation, infection, or malignancy. AGP is the primary carrier for basic (cationic) and neutral lipophilic drugs in human blood, contrasting with albumin, which primarily binds acidic molecules. In clinical pharmacology, AGP is a critical determinant of the pharmacokinetics of numerous therapeutic agents, including beta-blockers, local anesthetics, and tyrosine kinase inhibitors. Because only the unbound fraction of a drug is typically capable of exerting a therapeutic effect, changes in AGP levels can lead to significant alterations in drug efficacy and toxicity. For instance, elevated AGP levels in cancer patients can reduce the free fraction of chemotherapy agents, potentially leading to treatment resistance, while low levels in patients with hepatic impairment may increase the risk of adverse effects from highly protein-bound drugs.

Other names

OrosomucoidORMAlkaloid-binding globulinBasic drug-binding proteinORM1ORM2

Alpha-1-acid glycoprotein acts as a high-affinity, low-capacity binding protein for basic (alkaline) and lipophilic drugs in the plasma. By sequestering these molecules, it regulates their free (pharmacologically active) fraction, thereby influencing their distribution, metabolism, and overall pharmacokinetic profile (Katzung, B. G., Basic & Clinical Pharmacology, 14th Ed).