title: ECG changes and plasma concentrations of propafenone and its metabolites in a case of severe poisoning.
abstract: Propafenone is a class IC antiarrhythmic agent metabolized into two major metabolites, 5-hydroxypropafenone and N-depropylpropafenone. The potency of 5-hydroxypropafenone to block fast sodium channels is comparable to that of its parent. We report the positive correlation 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 propafenone were in the toxic range and correlated with the widening of the QRS-complex. The slow decline in concentration during this first phase might relate to saturation of the isoenzyme CYP2D6. The half-life of propafenone, calculated from the second phase, was approximately 3 hours, defining the patient as a fast metabolizer. The initial concentrations of the metabolite N-depropylpropafenone were surprisingly higher than those of 5-hydroxypropafenone which may also be due to saturation of CYP2D6.
authors.affiliation: University Hospital of Ghent, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Fonck
authors.forename: C
authors.initials: C
authors.lastname: Haenebalcke
authors.forename: A
authors.initials: A
authors.lastname: Hemeryck
authors.forename: F
authors.initials: F
authors.lastname: Belpaire
authors.forename: L
authors.initials: L
authors.lastname: Jordaens
authors.forename: P
authors.initials: P
authors.lastname: Calle
authors.forename: W
authors.initials: W
authors.lastname: Buylaert
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000506:poisoning*; D002851:Chromatography, High Pressure Liquid; D004562:Electrocardiography; D005260:Female; D006207:Half-Life; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D011041:Poisoning / Q000097:blood* / Q000628:therapy; D011405:Propafenone / Q000031:analogs & derivatives / Q000097:blood / Q000506:poisoning*
chemical_list: D000889:Anti-Arrhythmia Agents; D011405:Propafenone; C044307:5-hydroxypropafenone; C045806:N-depropylpropafenone