When protein binding is taken into account, the following relationship that describes the hepatic clearance of drugs can be obtained :
The effect of the change in protein binding on the hepatic clearance of drugs is dependent on the drug characteristics :
a- High extraction ratio drugs:
The elimination of these drugs is dependent on the hepatic blood flow and the change in protein binding does not affect their hepatic elimination.
The change in protein binding due to displacement from the binding sites does not affect the elimination rate of high extraction ratio drugs such as verapamil (90% bound), propranolol (87% bound), lidocaine (70% bound), and morphine (35% bound). This is because the extraction of these drugs by the liver is high and the drug molecules can be stripped from their binding sites in the liver.
