Mechanism of Plasma Protein Binding
Reversible Binding: Drugs form non-covalent interactions (e.g., hydrophobic, hydrogen bonding, electrostatic) with plasma proteins, maintaining a dynamic equilibrium between bound and free drug.
Competition for Binding Sites: Multiple drugs can bind to the same site, leading to displacement and increased free drug concentration, potentially enhancing drug effects or toxicity.
Influence on Pharmacokinetics: High protein binding reduces volume of distribution (Vd) and slows drug clearance, prolonging half-life.
Types of Plasma Proteins Involved in Drug Binding
Albumin: Binds primarily to acidic and neutral drugs; the most abundant plasma protein.
Alpha-1-Acid Glycoprotein (AAG): Binds mainly to basic drugs; concentration varies with disease or stress.
Lipoproteins: Transport lipophilic drugs, affecting their distribution and elimination.
Globulins: Some globulins, like sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG), transport specific hormones and drugs with similar structures.
Fibrinogen: Involved in blood clotting, with a minor role in drug binding.
