A drug X has affinity to bind with albumin and V has 150 times more affinity to bind with albumin than X. TRUE statement is (AIPG 2012)
|A||Drug X will available more in tissues|
|B||Drug Y will be more available in tissues|
|C||Free conc. of drug X in blood will be more|
|D||Toxicity of Y will be more|
In the question drug, X has 150 times lower affinity to bind with albumin than drug Y and it is clearly given in the book that highly plasma protein bound drugs are largely restricted to the vascular compartment and tends to have lower volume of distribution.
Option 'c' is confusing but the fact is that free concentration of the drug does not depend upon the plasma protein binding.
Other important aspects of plasma protein binding:
- The bound fraction is not available for action. However, it is in equilibrium with the free drug in plasma and dissociates when the concentration of the latter is reduced due to elimination. Plasma protein binding thus implies to temporary storage of the drug.
- High degree of protein binding generally makes the drug long acting, because bound fraction is not available for metabolism or excretion, unless it is actively extracted by liver or kidney tubules.
- Generally expressed plasma concentrations of the drug refer to bound as well as free drug.
- One drug can bind to may sites on the albumin molecule. Conversely, more than one drug can bind to the same site. This can give rise to displacement interactions among drugs bound to the same site.
- In nephrotic syndrome, binding may be reduced and high concentrations of free drug may be attained, eg phenytoin and furosemide.