Protein binding

Only the unbound fraction of a drug is really available to exert its pharmacological action by interaction with the therapeutic target or is available to undergo elimination processes.

Protein binding has a main impact in multiple aspects that condition drug properties. Protein binding can influence the distribution, can reduce the metabolic clearance by the liver, can limit the blood brain barrier permeability, can influence dosing regimens… Therefore, the binding of a new compound to plasma proteins, to relevant tissue or to red blood cells is critical to understand its properties.

Species differences  in plasma protein binding should also be known to explain differences in pharmacological activity or in safety, and for the prediction of human pharmacokinetics based on preclinical species data.