Protein Binding

The reversible binding of drug with non-specific and non-functional site on the body protein without showing any biological effect is called as protein binding. A drug’s efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse cell membranes or diffuse.

A drug molecule to less or more extent has a capacity to enter into specific combination with plasma protein. These molecular fractions play an important role in deciding the availability of drug for biotransformation, pharmacological site and excretion. Depending upon whether the drug is a weak or strong acid, base or is neutral, it can bind to a single blood protein to multi proteins. Common blood proteins that drugs bind to are albumin, lipoprotein, glycoprotein, and α, β and γ  globulins.

The most significant protein involved in the binding of drug is albumin, which comprises more than half of blood volume. Albumin interacts with acidic or basic drugs in the plasma by Vander – Waal’s force, hydrophobic binding, hydrogen bonding and ionic interaction. Acid – glycoprotein interacts with basic entities and lipoproteins bind with both basic and neutral drugs.

Factor Affecting Protein Binding

1. Lipophilicity is the most desirable physiochemical parameters that favour protein binding to occur. Also, an increase in the lipid content of drug moiety eventually enhances the rate as well as extends of protein binding process. For example, intramiscular Injection of Cloxacillin displays 95%  protein binding due to its greater lipophilicity.
2. Alteration in the concentration of drug substance as well as the protein molecules or surfaces subsequently brings alteration in the protein binding process.
3. Drug’s affinity towards specific protein/tissue is also an important factor for activity of the drug. For example, Digoxin has more affinity for cardiac muscles proteins as compared to that of proteins of skeletal muscles or those in the plasma.