Common blood proteins that drugs bind to are human serum albumin, lipoprotein, glycoprotein, and α, β‚ and γ globulins.
The bound portion may act as a reservoir or depot from which the drug is slowly released as the unbound form.
Since the unbound form is being metabolized and/or excreted from the body, the bound fraction will be released in order to maintain equilibrium.
This is significant because various medical conditions may affect the levels of albumin, alpha-1 acid glycoprotein, and lipoproteins.
Changes in the levels of free drug change the volume of distribution because free drug may distribute into the tissues leading to a decrease in plasma concentration profile.
For the drugs which rapidly undergo metabolism, clearance is dependent on the hepatic blood flow.
However, this effect is really only noticeable in closed systems where the pool of available proteins could potentially be exceeded by the number of drug molecules.
Biological systems, such as humans and animals, are open systems where molecules can be gained, lost or redistributed and where the protein pool capacity is almost never exceeded by the number of drug molecules.
Since a low therapeutic index indicates that there is a high risk of toxicity when using the drug, any potential increases in warfarin concentration could be very dangerous and lead to hemorrhage.