The pharmacokinetics of pirmenol during short term oral dosing

The clinical use of currently available antiarrhythmic agents has been plagued with numerous problems. Many arrhythmias, particularly recurrent ventricular tachycardia are frequently not controlled with these drugs. If these drugs are efficacious, chronic dosing often produces adverse effects which are serious or intolerable to the patient. Dosage schedules are often inconvenient due to the limited duration of effect. Moreover, oral dosage forms are not available for some antiarrhythmic agents. Pirmenol is an investigational antiarrhythmic agent which possesses electrophysiologic actions similar to the existing Type 1 agents, quinidine, procainamide and disopyramide. The drug is structurally similar to disopyramide. Pirmenol has been demonstrated to suppress premature ventricular contractions in animals and humans. Reported side effects have been minimal. In a post-infarction coronary ligated Harris dog model, Pirmenol administered intravenously, intramuscularly, or orally resulted in prompt conversion of ventricular arrhythmias to normal sinus rhythm. It was also effective in reversing ouabain and epinpherne-induced ventricular arrhythmias and aconitine-induced atrial arrhythmias. The drug did not interfer with electroconversion to normal sinus rhythm and ventricular fibrillation threshold was elevated. Effects on cardiac conduction were minimal at therapeutic doses. Some transient myocardial depression manifested as an increase in heart rate and decrease in contractility was noted and felt to be secondary to rapid infusion of the drug. The cardiac output was maintained.