What is Protein Binding?
Protein binding generally refers to the binding of a drug to proteins in blood plasma. The interaction can also be between the drug and tissue membranes, red blood cells, and other components of the blood. The amount of drug bound to protein determines how effective the drug is in the body. The bound drug is kept in the blood stream while the unbound components of the drug may be metabolized or extracted, making them the active part of the drug. So, if a drug is 95% bound to a binding protein and 5% is free, that means that 5% of the drug is active in the system and causing pharmacological effects.
Protein binding is often reversible and thus creates a chemical equilibrium, in which the chemical reaction can go backward and forward with no net change in reactants and products. This means that a cell that is effective at extracting the unbound drug may extract more of the drug as it disassociates in the course of achieving equilibrium. The equation for reversible protein binding is: Protein + drug ⇌ Protein-drug complex
The proteins commonly involved with protein binding are albumin, lipoproteins, and al-glycoprotein. A protein is a chain of amino acids joined by peptide bonds. Acidic drugs will tend to bind to albumin, which is basic and basic drugs will primarily bind to al-glycoprotein, which is acidic. Acidic drugs may also bind to lipoproteins if the albumin is saturated. Lipoprotein binding is not binding in the strict sense of the term; it is closer to dissolving and is common in lipid soluble drugs. A drug that binds to tissue often binds to melanin-rich tissue or DNA.
The amount of protein binding and the fraction unbound, written as the concentration of unbound drug over the total concentration of the drug, depends on several factors. It is determined by the drug’s affinity for the protein, the concentration of the binding protein, and the concentration of the drug relative to the binding protein. This is important when considering other medications that a patient might be on because certain proteins may already be saturated, which would affect the amount of free drug and possibly change the desired pharmacologic effects.
For example, if drug A saturated a certain binding protein and then drug B was not able to bind to that protein, then there would be a higher concentration of unbound drug B. Drug B could also competitively displace drug A from the binding protein, thus raising the unbound fraction of drug A. This process happens fairly quickly, in minutes to hours, and both scenarios could have adverse effects. Many drugs, however, have different binding proteins, different binding sites on a protein, or are not present in high enough relative concentration to saturate the proteins, and so do not compete with the other drug or drugs in use.
Likewise, the ability of the body to extract the drug can affect the drug’s clearance into the body. Renal failure and liver disease often negatively impact the body’s ability to extract the unbound drug. For these reasons, it is important to consider previous medical issues, the total concentration of the drug, the unbound fraction of the drug, and any other medications a patient may be taking.
Written by Caitlin Kenney
