Drug Binding to Plasma Proteins

Abstract

After absorption, most drugs will distribute heterogeneouslyacross tissues and organs, with the total drug concentration in plasmagenerally not being representative of the total concentration in other tissues.The main factors that explain the non-homogeneous distribution are the affinityof the drug for drug transporters and/or for tissue constituents. In plasma,drug molecules can reversibly interact with plasma proteins (mainly albumin, α1-acidglycoprotein (AAG), and, to a lesser extent, lipoproteins). Due to its size,the complex between the drug and a plasma protein cannot readily leave theintravascular space through transcellular diffusion across the endothelia. Thefree drug theory assumes that only the unbound drug fraction freely permeatesthrough biological barriers, directly contributing to drug distribution: ifcertain assumptions are met (e.g., absence of active transport), only unbounddrug concentrations will be equal at steady state.