Influence of serum proteins on erythrocyte uptake of digoxin and digitoxin

My purpose was to find out whether changes in serum protein content (albumin and gamma globulin) influenced erythrocyte uptake of glycosides and the capacity of erythrocytes to equilibrate glycoside levels when there are changes in protein binding. Heparinized human blood was incubated with 3H-digoxin, 6 ng/ml, and 3H-digitoxin, 44 ng/ml for 15 min. After centrifugation, distribution between plasma and erythrocytes was determined by liquid scintillation. Ratios between erythrocyte and plasma concentrations were 0.84 and 0.11 for digoxin and digitoxin. Replacing plasma by a protein-free isotonic solution led to increased erythrocyte uptake by 15% and 540% for digoxin and digitoxin. Erythrocyte uptake for both drugs was also determined in varying amounts of albumin (0 to 120 gm/l) and gamma globulin (0 to 25 gm/l). Only albumin influenced the erythrocyte uptake of these drugs. Calculations of free and bound plasma levels for both drugs showed that free digitoxin increased when albumin concentrations were equal to or less than 10 gm/l and remained constant (3%) for albumin concentrations between 15 and 120 gm/l. Free digoxin plasma levels rise when the albumin concentration is equal to or less than 15 gm/l and do not change at albumin levels between 30 and 120 gm/l. These data indicate that blood components play an important role in equilibrating changes in free digoxin and digitoxin levels.