Drug Binding in Plasma

Abstract

The ligands are generally bound in plasma to a significant extent by several transport proteins (both high and low affinity), irrespective of their endogenous or exogenous origin. The protein binding of endogenous compounds (such as hormones) exhibits higher affinity and specificity than those of exogenous compounds (such as drugs). For plasma proteins that bind the same ligand(s), structural similarities or a common genetic origin may be found, although this is not a general rule. Alterations in ligand binding may be due to modifications of either the structure or the level of the binding protein. These modifications may result from genetic make up, physiology or pathology. In some situations, plasma binding may impair the distribution of drugs to tissues, with drug distribution then mainly restricted to the distribution compartment of the drug-binding protein. In other instances, the plasma drug-binding is permissive, and does not limit drug distribution to tissues. A given drug-transport protein system may have either a permissive or a restrictive effect on the drug distribution, depending on the tissue. The physiological significance of the high-affinity transport proteins is not completely understood. These proteins may increase the plasma concentration of poorly hydrosoluble ligands, ensure a more uniform tissue distribution and increase the life of the ligands. The life of the protein may also be increased by ligand binding. High-affinity transport proteins are also involved in some specific carrier mediated transfer mechanisms. It is possible to demonstrate structure-binding relationships or binding selectivity for the plasma transport proteins, but these are quite independent of relationships observed at the receptor level.

Application of Solid Phase Microextraction for Quantitation of Polyunsaturated Fatty Acids in Biological Fluids

“…Amount of FAs extracted from spiked standard human albumin solutions were plotted against the protein concentrations (C p ), and the K a was determined by fitting equation 2 through the data points. 57 …”

In silico ADME modeling: QSPR models for the binding of β- lactams to human serum proteins using genetic algorithms

“…Thus, the higher the protein binding, the lesser is the metabolic clearance of the drug, especially, when the binding is restrictive 27 Thus, an increase in the lifetime of the drug is observed for strongly binding drugs. Hence, the greater accuracy of prediction of high binding percent of drugs is desirable, as even small errors in this range will have significant impact on the pharmacodynamic effect of the drug.…”

“…Albumin is the protein of highest concentration in the serum (plasma is serum plus clotting proteins). It is a carrier of many small molecules, 8 and is very important in maintaining the oncotic pressure of the blood (that is keeping the fluid from leaking out into the tissues). Binding of a drug to serum proteins in human plasma is a major determinant of its pharmacodynamic behavior (the action of a drug to the body) and the pharmacokinetics of the experience and intuition are the key factors for success.…”

Synthesis and Characterization of TiO2 Nanoparticles: Applications in Research on the Interaction of Colloidal TiO2 with Human Serum Albumin by Fluorescence Spectroscopy

“…It contributes significantly to colloidal osmotic blood pressure and to many transport and regulatory processes. 7 The binding properties of HSA with drugs have been investigated by many researchers. [8][9][10][11][12] HSA is a water-soluble protein with a molecular weight of 66500, which includes 585 amino-acid residues.…”