The extent to which a drug is bound to plasma protein determines the fraction of drug that is active or which can be extracted by the eliminating organ(s). Altered binding will change the various kinetics significantly only if they are limited to free drug in plasma.
Parameters:
(1) total plasma drug concentration
(2) bound or unbound (free) plasma drug concentration
unbound fraction =
= (unbound drug concentration) / (total drug concentration)
bound fraction =
= 1 - (unbound fraction)
Interpretation:
• An unbound fraction < 0.1 indicates a drug that is highly bound.
Considerations when there is high protein binding:
(1) The free drug fraction should be measured in addition to the total, since the free drug concentration is the amount available.
(2) A decrease in the maintenance dose will be necessary:
(2a) if the total protein concentration is decreased
(2b) if there is a increase in a drug that competes for the protein binding sites
(2c) if there is improvement in a disease with lower levels of metabolites competing for binding sites
(3) An increase in the maintenance dose will be necessary:
(3a) if the total protein concentration increases
(3b) if there is a decrease in a drug that competes for protein binding sites
(3c) if there is a deterioration in a disease with higher levels of metabolites competing for binding sites
