3.12:
Drug Distribution: Plasma Protein Binding
Most drugs are primarily bound to plasma proteins such as albumin, with only a small fraction remaining unbound. This unbound free fraction is equal to one minus the fraction that is bound.
Acidic drugs reversibly bind to plasma albumin to form large, inactive complexes that are incapable of diffusing across biological barriers.
Such drug-protein complexes serve as drug reservoirs. When the concentration of free drugs declines, the complexes rapidly dissociate, releasing the free drug and maintaining the free fraction.
The amount of protein-bound drugs is influenced by the concentration of free drug and protein, the number of binding sites and the affinity between the drug and the binding sites.
Different drugs or endogenous substances can competitively bind to plasma proteins.
For example, the competitive binding of sulfonamide reduces albumin's affinity for bilirubin, causing the release of free bilirubin. This can increase the risk of bilirubin encephalopathy in newborns.
Similarly, during exercise, fat metabolism releases high concentrations of free fatty acid into the plasma. These fatty acids displace the drugs bound to albumin and increase the concentration of free drugs.
3.12:
Drug Distribution: Plasma Protein Binding
Drugs predominantly attach to plasma proteins, with only a small percentage remaining unbound. The unbound portion can be calculated as one minus the bound fraction. Acidic drugs form large, inactive complexes by reversibly binding to plasma albumin, which prevents them from diffusing across biological barriers. These drug-protein complexes act as reservoirs for the drugs. As the concentration of unbound drugs decreases, these complexes quickly dissociate to release the free drug, maintaining the unbound fraction. The quantity of protein-bound drugs relies on various factors, including the concentrations of free drug and protein, the number of binding sites, and their affinity for the drug. Due to the abundance of binding sites and indiscriminate binding, various drugs or endogenous substances may engage in competitive binding with plasma proteins. For instance, when sulfonamide competitively binds to plasma proteins, it reduces albumin's affinity for bilirubin, releasing free bilirubin and increasing the risk of bilirubin encephalopathy in newborns. In situations like exercise or infection, where free fatty acid concentrations in plasma are elevated, drugs bound to albumin may be displaced, raising the concentration of unbound drugs.