Relationship between the pharmacokinetics of a short-acting antiarrhythmic drug and its effects: studies with Falirytmin

Abstract

Pharmacokinetics, and the effect on cardiac conduction times were studied in ten patients after intravenous infusion (50 mg) of the new antiarrhythmic N,N'-Bis-[3-(2'-aethoxyphenoxy)-2-hydroxypropyl]-aethylendiamin (Falirytmin). The change of the PA, AH and HV interval induced by the drug was measured by the His-bundle electrogram technique. The results were compared with those of a previous study where the atrioventricular conduction time (PQ-interval) had been measured non-invasively. A 2-compartment open model was fitted to the measured blood concentrations. A total body clearance close to 1500 ml/min was calculated in both studies. An average biological half-life of 18.2 and 13.9 min, respectively, was found. The significant delay which was observed between the time course of blood concentration and response vanished if the change in conduction time was set in comparison to the theoretical drug amount in the peripheral compartment of the model.