What role does plasma protein binding play in drug distribution?

Plasma protein binding plays a significant role in drug distribution by limiting the distribution of drugs to target tissues. When a drug is administered, it can bind to proteins in the plasma, such as albumin or globulins. The portion of the drug that binds to these proteins is generally not active because it is not free to exert its therapeutic effects. As a result, only the unbound or free drug can diffuse from the bloodstream into tissues where it can interact with receptors or have pharmacological effects.

This binding affects the distribution equilibrium between the blood and various tissues, leading to a reduced concentration of the free drug available for therapeutic activity in those tissues. A drug that is highly bound to plasma proteins will have a lower volume of distribution because it's more "trapped" within the bloodstream, while a drug with low protein binding will distribute more freely into the tissues.

In summary, the role of plasma protein binding in drug distribution is critical for controlling the bioavailability of the drug, influencing how much of it gets to the target site, and thereby impacting drug efficacy and safety.