Toxicokinetic-toxicodynamic models describing the relation of plasma and red blood cell potassium with plasma digitalis in acute human digitalis poisoning

Abstract

Toxicity of cardiac glycosides involves the inhibition of the Na +-K + ATPase pump. As a consequence, extracellular K + concentration rises and intracellular K + concentration strongly decreases. Red blood cell (RBC) K + is a practical marker of ATPase inhibition. In a group of 15 patients intoxicated by digitoxin and lanatoside C, correlations between the calculated digitoxin ingested dose or plasma digitoxin levels and the kinetics of plasma K + and RBC K + have been assessed using kinetic-effect modelling. A correlation between the calculated ingested dose of digitoxin with RBC K + was found ( r = 0.64). A direct relation based on the linear model fitted the relation between extracellular K + and digitalis concentration. An indirect relation based on the Emax sigmoid model fitted the relation between RBC K + and digitoxin concentrations. Specific parameters were obtained from the linear model with a = 0.0196 ± 0.0272 and b = 0.455 ± 0.035. Specific parameters were derived from the Emax sigmoid model with k eo = 0.0139 ± 0.0052/hr and EC 50 = 91.95 ± 20.55 ng/ml, where k eo = first-order rate constant of the disappearance of the toxic effect and EC 50 = digitoxin concentration decreasing the RBC K + concentration by 50%. These data showed that the in vitro assays of plasma K + and RBC K + are convenient and predictive assays for evaluating the severity of human digitoxin poisoning.