02.02.2 Protein Binding

Plasma proteins, such as albumin and globulin, were not designed to carry drugs, but are quite effective at doing so. Acidic drugs bind to albumin, whereas basic drugs bind to globulin. In the plasma there is equilibrium between the protein-bound and free drug (Figure 2.1).

Figure 2.1 Protein binding and distribution (Copyright QUT, Sheila Doggrell)

The bound drug cannot leave the blood stream whereas the free drug can leave the circulation, often to have its pharmacodynamic effect. When free drug leaves the blood vessel, more drug is released from the binding, to maintain the equilibrium. Thus, drug is gradually being released from plasma proteins.

Bilirubin is a yellow breakdown product from red blood cells. Bilirubin binds to albumin. In liver disease, the levels of bilirubin may be high, giving the condition known as jaundice. High levels of bilirubin will also displace drugs from binding to plasma proteins. Thus, the blood levels of free drug may increase in jaundice, with the effect of the drug going from therapeutic to toxic. Thus, in jaundice, the doses of some drugs have to be decreased.

In addition to bilirubin, drugs can compete for the same site on the plasma protein (Figure 2.2).

Figure 2.2 Drugs competing for binding site (Copyright QUT University, Sheila Doggrell)

Figure 2.2 shows drugs A and B competing for the same binding site on a plasma protein. Aspirin and warfarin are examples of drugs that have the same binding site on a plasma protein. Aspirin and warfarin are often used together in cardiovascular disease. Warfarin is used as an anti-coagulant, and the anti-coagulant effect is dependent on the free concentration of warfarin. When aspirin displaces warfarin from their binding site, the free concentration of warfarin will be increased, and there may be too much anti-coagulation, which may lead to haemorrhage. Thus, when aspirin and warfarin are given to a person, it may be necessary to reduce the dose of warfarin.