Dear Sidharta,

The equilibrium of Drug + Protein = Drug-Protein is very important in pharmacology because of the following:

1-If the ratio of [Drug] free/[Drug]bound is very large the possibility of toxicity from the drug is high, and the effect of the drug is very potent.

2-The Drug-protein complex serves as a device for a controlled release of the drug.

3-The affinity of the drug to protein plays a dominant role in the toxicity since if a certain drug has a very strong affinity to protein it can compete with another drug having low affinity which results in a high concentration of the latter drug in the blood circulation (over dosing and consequently toxicity).

4-If the binding affinity of a drug to protein is very high, the time in which the drug reaches its active site will be very long, thus making the drug ineffective.

Hoping this will be helpful,

Rafik

Protein binding displacement interactions and their clinical importance.

McElnay JC, D'Arcy PF.

Abstract

The binding of drugs to proteins is an important pharmacokinetic parameter. Many methods are available for the study of drug protein binding phenomena and there are also many ways to interpret the binding data. Although much emphasis has been placed on the binding of drugs in the plasma, binding also takes place in the tissues. Displacement interactions involving plasma or tissue binding sites have been implicated as the causative mechanisms in many drug interactions. However, the importance of plasma binding displacement as a mechanism of drug interactions. However, the importance of plasma binding displacement as a mechanism of drug interaction has been overestimated and overstated, being based largely on in vitro data. Because displaced drug can normally distribute out of the plasma compartment, increases of free drug concentrations are usually transient and therefore will not give rise to changed pharmacological effects in the patient. Those clinically important drug interactions formerly considered to be caused via displacement from plasma binding sites usually have another interaction mechanism involved; commonly decreased metabolism or renal elimination also takes place. Plasma binding displacement interactions, however, do become important clinically in certain specific situations, namely, when the displacing drug is administered quickly to the patient by the intravenous route, during therapeutic drug monitoring, and in certain drug disposition studies which involve the use of a heparin lock for blood sampling. Tissue binding displacement interactions have a greater potential to cause adverse effects in the patient as in this case drug will be forced from extravascular sites back into the plasma. The resulting increased drug plasma levels will lead to enhanced pharmacological effects and, possibly, frank toxicity. Displacement of drugs from binding sites simultaneously in both the plasma and in the tissues will combine the effects seen after displacement from the separat

http://www.ncbi.nlm.nih.gov/pubmed/6345130

http://link.springer.com/article/10.2165/00003495-198325050-00003

Read the book COMPETITIVE PROTEIN BINDING by Yalow and Bergson, nobel prize