Erythrocyte Na⁺, K⁺-ATPase and serum digoxin concentrations

Digoxin therapy has been made more rational by the measurement of serum digoxin concentrations. However, difficulties remain because of the overlap between "therapeutic" and "toxic" serum concentrations and the lack of an obvious therapeutic endpoint in many patients. An assay which measures the degree of interaction between digoxin and its putative receptor, the membrane Na⁺, K⁺-ATPase, might be capable of resolving some of these difficulties. Therefore, as a first approach in this direction we evaluated the relationship between serum digoxin concentration and the degree of inhibition of RBC ghost Na⁺, K⁺-ATPase activity in patients receiving digoxin therapy. Utilizing an improved micro-assay technique, Na⁺, K⁺-ATPase activity was determined in aliquots of RBC ghosts before and after removal of bound digoxin. In 27 patients a significant relationship was present between serum digoxin concentration and the degree of RBC ghost Na⁺,K⁺-ATPase inhibition. However, at any serum digoxin concentration, there was a variation in the magnitude of enzyme inhibition from patient to patient. This study confirms the feasibility of determining the degree of in vivo RBC Na⁺,K⁺-ATPase inhibition in man and demonstrates, for the first time, a highly significant but somewhat variable relationship between serum digoxin concentrations and the magnitude of RBC digoxin receptor inactivation. This quantitative, functional, individualized assay of digoxin effects may prove to be of clinical value in the future.