Clinical Effects and Pharmacokinetics of a Single Oral Dose of Pirmenol Hydrochloride

• Published in: Journal of cardiovascular pharmacology Vol. 27; no. 4; pp. 556 - 562
• Main Authors: Atarashi, Hirotsugu, Kuruma, Akinori, Ino, Takesi, Hirayama, Yosiyuki, Saitoh, Hirokazu, Hayakawa, Hirokazu
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Lippincott-Raven Publishers 01-04-1996; Hagerstown, MD Lippincott
• Subjects: Administration, Oral; Adult; Anti-Arrhythmia Agents - pharmacokinetics; Anti-Arrhythmia Agents - therapeutic use; Antiarythmic agents; Atrial Fibrillation - drug therapy; Biological and medical sciences; Cardiovascular system; Female; Hemodynamics - drug effects; Humans; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Piperidines - blood; Piperidines - pharmacokinetics; Piperidines - therapeutic use; Tachycardia, Atrioventricular Nodal Reentry - drug therapy; Tachycardia, Supraventricular - drug therapy; Tachycardia, Supraventricular - etiology; Human; Arrhythmia; Atrial fibrillation; Single dose; Oral administration; Electrophysiology; Cardiovascular disease; Paroxysmal supraventricular tachycardia; Excitability disorder; Chemotherapy; Treatment; Heart disease; Hemodynamics; Pharmacokinetics; Antiarrhythmia agent
• ISSN: 0160-2446; 1533-4023
• DOI: 10.1097/00005344-199604000-00015

To establish the clinical efficacy of a single oral dose of pirmenol, we evaluated electrophysiologic and hemodynamic effects simultaneously after drug administration, performing electrophysiologic testing in 20 patients with ECG-documented paroxysmal supraventricular tachycardia (PSVT) before and after a single oral 200-mg dose of pirmenol. Hemodynamic measurements were made with a Swan-Ganz catheter in the first 10 consecutive patients. In a different series of patients, we administered a single 200-mg oral dose of pirmenol to evaluate its acute termination effect in 7 patients with PSVT and 9 with paroxysmal atrial fibrillation. Pirmenol prolonged the refractory period of the retrograde conduction system in patients with or without an accessory pathway, and supraventricular tachycardia was no longer inducible at 60 min in 11 patients [8 of 11 with atrioventricular (AV) reentrant tachycardia and 3 of 5 with AV nodal reentrant tachycardia]. Pirmenol increased the heart rate (p < 0.01) and total systemic resistance (p < 0.05), and reduced the stroke volume index (p < 0.01), all significantly. The plasma concentration of pirmenol at 1 h after administration was 0.75 ± 0.48 μg/ml. A single oral dose of pirmenol during tachyarrhythmia successfully restored sinus rhythm in 4 of 7 (57%) patients with PSVT and 4 of 9 (44%) patients with paroxysmal atrial fibrillation. A single oral dose of pirmenol was well tolerated as episodic treatment in patients with supraventricular tachyarrhythmias.