• Bruno Mégarbane, Arsia Amir Aslani, Nicolas Deye, and Frédéric J Baud.
• Hôpital Lariboisière, Réanimation Médicale et Toxicologique, 2 rue Ambroise Paré, 75010, Paris, France. bruno-megarbane@wanadoo.fr
• Expert Opin Drug Metab Toxicol. 2008 May 1;4(5):569-79.

BackgroundHypotension, cardiac failure, QT interval prolongation, dysrhythmias, and conduction disturbances are common complications of overdoses with cardiotoxicants. Pharmacokinetic/pharmacodynamic (PK/PD) relationships are useful to assess diagnosis, prognosis, and treatment efficacy in acute poisonings.ObjectiveTo review the utility and limits of PK/PD studies of cardiac toxicity.MethodsDiscussion of various models, mainly those obtained in digitalis, cyanide, venlafaxine and citalopram poisonings.Results/ConclusionsA sigmoidal E(max) model appears adequate to represent the PK/PD relationships in cardiotoxic poisonings. PK/PD correlations investigate the discrepancies between the time course of the effect magnitude and its evolving concentrations. They may help in understanding the mechanisms of occurrence as well as disappearance of a cardiotoxic effect. When data are sparse, population-based PK/PD modeling using computer-intensive algorithms is helpful to estimate population mean values of PK parameters as well as their individual variability. Further PK/PD studies are needed in medical toxicology to allow understanding of the meaning of blood toxicant concentration in acute poisonings and thus improve management.

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