Electrophysiologic and Hemodynamic Effects of a Single Oral Dose of Pilsicainide Hydrochloride, a New Class 1c Antiarrhythmic Agent

• Published in: Journal of cardiovascular pharmacology Vol. 31; no. 1; pp. 157 - 164
• Main Authors: Ino, Takeshi, Atarashi, Hirotsugu, Kuruma, Akinori, Onodera, Takeo, Saitoh, Hirokazu, Hayakawa, Hirokazu
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Lippincott-Raven Publishers 01-01-1998; Hagerstown, MD Lippincott
• Subjects: Administration, Oral; Adult; Anti-Arrhythmia Agents - administration & dosage; Anti-Arrhythmia Agents - blood; Anti-Arrhythmia Agents - pharmacokinetics; Anti-Arrhythmia Agents - pharmacology; Antiarythmic agents; Atrial Function - drug effects; Biological and medical sciences; Cardiovascular system; Electrocardiography; Electrophysiology - methods; Female; Heart - drug effects; Heart - physiology; Hemodynamics - drug effects; Humans; Lidocaine - administration & dosage; Lidocaine - analogs & derivatives; Lidocaine - blood; Lidocaine - pharmacokinetics; Lidocaine - pharmacology; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Tachycardia, Supraventricular - blood; Tachycardia, Supraventricular - chemically induced; Tachycardia, Supraventricular - prevention & control; Human; Pharmacokinetic pharmacodynamic relationship; Arrhythmia; Toxicity; Treatment efficiency; Single dose; Oral administration; Electrophysiology; Cardiovascular disease; Paroxysmal supraventricular tachycardia; Antiarrhythmic agent; Excitability disorder; Pilsicainide; Heart disease; Secondary effect; Effective dose; Hemodynamics; Mechanism of action; Anilide
• ISSN: 0160-2446; 1533-4023
• DOI: 10.1097/00005344-199801000-00021

To establish the clinical efficacy of pilsicainide, we evaluated its electrophysiologic and hemodynamic effects after a single oral administration to 18 patients with documented supraventricular tachycardia (SVT). To determine the minimal effective blood level, changes in efficacy with time were evaluated by serial reinduction studies with venous blood sampling for measurement of the plasma pilsicainide level. Sixty minutes after administration of a single oral dose of pilsicainide, the sinoatrial conduction time, AH and HV intervals, and the effective refractory period of the right ventricle were prolonged. Ventriculoatrial conduction was blocked in 11 patients [nine of 12 via accessory pathway and two of six via the atrioventricular (AV) node], resulting in the suppression of SVT induction in nine of 13 patients. Pilsicainide increased the heart rate and mean pulmonary arterial pressure and decreased the stroke volume index at 60 min. PQ interval, QRS width, and QTc were significantly prolonged after pilsicainide, and the percentage prolongations of the PQ interval were well correlated with the plasma pilsicainide levels. The plasma level effective for suppression of SVT was considered to be >0.5 μg/ml. We concluded that a single oral administration of pilsicainide is well tolerated and effective in suppressing SVT.