ECG-CHANGES AND PLASMA-CONCENTRATIONS OF PROPAFENONE AND ITS METABOLITES IN A CASE OF SEVERE POISONING

Case Report: Propafenone is a class I-C antiarrhythmic agent metaboliz ed into two major metabolites, 5-hydroxypropafenone and N-depropylprop afenone. The potency of 5-hydroxypropafenone to block fast sodium chan nels is comparable to that of its parent. We report the positive corre lation between plasma concentrations and electrocardiographic changes in a patient with severe oral self-poisoning. Serial ECG changes were measured and plasma concentrations were determined by high-performance liquid chromatography. The initial plasma concentrations of propafeno ne were in the toxic range and correlated with the widening of the QRS -complex. The slow decline in concentration during this first phase mi ght relate to saturation of the isoenzyme CYP2D6. The half-life of pro pafenone, calculated from the second phase, was approximately 3 hours, defining the patient as a fast metabolizer. The initial concentration s of the metabolite N-depropylpropafenone were surprisingly higher tha n those of 5-hydroxypropafenone which may also be due to saturation of CYP2D6.