Concepts for Toxicokinetic-Toxicodynamic Modelling in Clinical Toxicology: Application to Acute Cardiac Glycoside Intoxications

Relationships between pharmacokinetics (PK) and pharmacodynamics (PD) are now widely investigated for many drugs with the aim of improving the amount and the rate of drug delivery so as to control the duration and intensity of the pharmacological effect (Levy 1966; Holford 1981). Such relationships have not yet been investigated for toxic effects of drugs as occurs after acute self-poisoning. The establishment of relationships between kinetics of drugs at toxic doses (Toxicokinetics) and those of their pharmacological effects (Toxicodynamics) can be of interest in clinical toxicology. The aim would be to predict the occurrence and the intensity of toxic effects as a function of the ingested dose and the first plasma concentrations on admission of the patient to improve management. In this paper, we describe the different techniques of kinetic-effect modelling actually available, their applications in the case of acute digitalis poisoning and the limits of such techniques in clinical toxicology.