title: Intravenous and oral propafenone for treatment of tachycardia in infants and children: pharmacokinetics and clinical response.
abstract: To elucidate contribution of an active metabolite to overall clinical responses to propafenone, steady-state disposition of propafenone and its active metabolite and the clinical responses to treatment were examined in pediatric patients receiving intravenous or oral propafenone. There were more than ten-fold interindividual differences in apparent clearance, resulting in a wide range of the steady-state trough plasma concentrations of propafenone. The active metabolite, 5-hydroxypropafenone, was detected in four of the six patients receiving oral propafenone; however, two neonates receiving oral propafenone and all eight receiving intravenous propafenone had no detectable levels of 5-hydroxypropafenone in plasma. In nine patients for whom electrocardiographic (ECG) data were available, the PQ interval was significantly increased, whereas the QRS duration and the QTc interval were not. There was no close relationship between plasma concentrations of propafenone or 5-hydroxypropafenone and ECG parameters. Lack of good correlation between serum concentrations and clinical response precludes using a serum-concentration targeting strategy with propafenone therapy.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, University of Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.forename: R
authors.initials: R
authors.lastname: Gow
authors.forename: Z
authors.initials: Z
authors.lastname: Verjee
authors.forename: E
authors.initials: E
authors.lastname: Giesbrecht
authors.forename: H
authors.initials: H
authors.lastname: Dodo
authors.forename: R
authors.initials: R
authors.lastname: Freedom
authors.forename: G R
authors.initials: GR
authors.lastname: Tonn
authors.forename: J E
authors.initials: JE
authors.lastname: Axelson
authors.forename: E
authors.initials: E
authors.lastname: Zalzstein
authors.forename: H C
authors.initials: HC
authors.lastname: Rosenberg
authors.forename: G
authors.initials: G
authors.lastname: Koren
mesh_terms: D000284:Administration, Oral; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D011405:Propafenone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013610:Tachycardia / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D011405:Propafenone; C044307:5-hydroxypropafenone