title: 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.
authors.affiliation: INSERM U 26, Hôpital Fernand Widal, 200 Rue du Faubourg Saint Denis, 75475 Paris, Cédex 10, France.
authors.forename: M
authors.initials: M
authors.lastname: Urtizberea
authors.forename: M
authors.initials: M
authors.lastname: Rochdi
authors.forename: F J
authors.initials: FJ
authors.lastname: Baud
authors.forename: J M
authors.initials: JM
authors.lastname: Scherrmann