Protein binding changes and drug interactions: What do we know?
What common disease states can cause hypoalbuminemia? Many disease states can result in low albumin levels. The most common ones are malnutrition, malignancies, stress, injury, burns, pregnancy, and diabetes.3 When there is less albumin to bind to, free drug levels may be increased.
Can AAG levels change with disease states as well? Because AAG accounts for a lower percentage of total plasma protein than albumin, there may be less clinical concern regarding AAG. AAG levels usually do not drop, but instead can become elevated during times of trauma, inflammation, and acute myocardial infarction. This could result in increased binding of the free drug.4Which medications bind to red blood cells (RBCs)? There are several locations for drugs to bind to RBCs, including to hemoglobin and the plasma membrane. Medications that commonly bind to RBCs include barbiturates, chlorpromazine, imipramine, and phenytoin.5
What are common highly-bound medications? The Table1 provides examples of medications that are >90% protein-bound. However, this information may be misleading because many medications are highly bound. Zhang et al1 compiled binding data for 222 drugs, half of which bind 90% to 100%. However, the literature does not indicate that they all have clinically significant interactions. Benet and Hoener6 discuss how factors other than protein binding affect potential drug interactions, and the complexity of the body’s ability to compensate for increased free drug. Medication characteristics that may contribute to producing a significant interaction include, but are not limited to:
- free vs protein-bound drug in the plasma or tissue
- volume of distribution
- organs affected
- hepatic bioavailability
- drug clearance.
For example, VPA is 93% protein-bound and phenytoin is 91% protein-bound.1 However, this interaction is affected by more than just protein binding. VPA not only displaces the protein-bound phenytoin, but also inhibits its metabolism, which together result in increased free phenytoin levels.
Continued to: Another area of concern is a critically ill patient...
