Drug-binding proteins in serum can fluctuate in disease states. This means that drug levels can change in unanticipated ways. For example, if albumin levels fall, as can occur in liver failure or nephrotic syndrome, less albumin will be available for drug binding. If this happens, a normal dose of the drug may now produce a toxic concentration of free drug since there is less albumin to bind the drug.
The accompanying figure illustrates the loss of equilibrium between a protein-bound drug and a free drug when drug-binding proteins are diminished.
Drugs that are highly protein-bound may need dose adjustments in patients with lower drug-binding protein levels. Examples of some common drugs that are highly protein-bound include thyroxine, warfarin, diazepam, heparin, imipramine, and phenytoin.
