b- Low extraction ratio drugs that are not highly bound to plasma protein (<75% bound ) :
The elimination of these drugs does not change significantly due to the change in protein binding.
The change in protein binding due to displacement from the binding sites for drugs such as procainamide (16% bound) or theophylline (55% bound) will cause small change in the free drug concentration. This does not lead to significant change in the rate of elimination of these drugs.
c- Low extraction ratio drugs that are highly bound to plasma protein (>75% bound ) :
The elimination rate of these drugs is very sensitive to the change in protein binding.
Small change in protein binding will cause significant change in the free drug concentration and will alter the liver ability to eliminate the drug. The change in protein binding due to displacement from the binding sites for drugs such as warfarin (99% bound), valproic acid (93% bound), or diazepam (98% bound) will cause a significant increase in the free drug concentration. (For example changing the binding of warfarin to 98% will result in 100% increase in the free warfarin conc). This will lead to significant increase in the rate of elimination of these drugs.
