title: Therapeutic monitoring of class I antiarrhythmic agents using high-resolution electrocardiography instead of blood samples.
abstract: Antiarrhythmic therapy requires monitoring of serum drug concentrations to determine a patient's optimal oral dose of medication. Repeated examination of blood samples, however, is costly and time-consuming, so the present study evaluated whether changes in serum concentrations could be estimated from changes in electrocardiographic (ECG) parameters. Of 36 patients receiving antiarrhythmic drugs for supraventricular or ventricular arrhythmias, 12 were treated with flecainide, 12 with pilsicainide, and 12 with pirmenol. Signal-averaged ECG (SAECG) were recorded before starting drug administration, 1 month later, and twice during ongoing therapy. At the time of the 2nd to the 4th recordings, serum concentrations of the drugs were also measured. As previously reported, all agents, but especially flecainide and pilsicainide, prolonged the filtered QRS (f-QRS) and the duration of low-amplitude signals at the terminal portion of the QRS complex. The SAECG parameters varied between the recordings made during therapy. Differences in the duration of the f-QRS between 2 recordings correlated significantly with differences in serum drug concentrations (r=0.91 for flecainide, r=0.70 for pilsicainide, and r=0.61 for pirmenol). No significant correlation between drug concentration and other SAECG parameters was found. Changes in the serum concentration of flecainide, pilsicainide and pirmenol can be estimated from changes in the duration of the f-QRS on the SAECG and periodic monitoring of such could help reduce the number of repeat measurements of drug concentrations in blood samples.
authors.affiliation: First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Igor
authors.initials: I
authors.lastname: Sutovsky
authors.forename: Takao
authors.initials: T
authors.lastname: Katoh
authors.forename: Hideo
authors.initials: H
authors.lastname: Takayama
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Ono
authors.forename: Teruo
authors.initials: T
authors.lastname: Takano
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000295:instrumentation / Q000379:methods*; D004562:Electrocardiography; D005260:Female; D005424:Flecainide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D008012:Lidocaine; C042288:pilsicainide; D005424:Flecainide; C024318:pirmenol