Sites of Drug Binding
Binding to Plasma Proteins

Many drugs are bound to plasma proteins. Most bind to albumin, although certain drugs bind to other plasma proteins. In general, binding is reversible and obeys the law of mass action:

(free drug) + (albumin) (drug-albumin complex)

where k1 and k2 are the association and dissociation rate constants, respectively.

At equilibrium:

where KD is the equilibrium dissociation constant. It is a measure of the affinity of the drug for albumin:

The lower the KD, the higher the affinity.
The higher the KD, the lower the affinity.


At low concentrations of drug (less than the KD), the fraction bound is largely a function of the concentration of binding sites and the KD. At high concentrations (greater than the KD), the fraction bound is largely a function of the number of binding sites and the drug concentration.

As the concentration of drug increases in plasma, the percent that is bound will decrease.


Other factors affecting binding:
  • Number of drug binding sites on the protein
  • Protein concentration
  • Lipid solubility
  • Weak acids are bound more extensively than weak bases
  • Competing molecules
  • Species variations
  • Disease