The effects of programmed ventricular stimulation on plasma procainamide levels: an experimental model

• Published in: Journal of clinical pharmacology Vol. 34; no. 2; p. 184
• Main Authors: Brautigam, R T, Porter, S, Kutalek, S P
• Format: Journal Article
• Language: English
• Published: England 01.02.1994
• Subjects: Animals; Blood Pressure - physiology; Disease Models, Animal; Dogs; Electric Stimulation; Electrocardiography; Myocardial Infarction - blood; Myocardial Infarction - physiopathology; Procainamide - administration & dosage; Procainamide - blood; Tachycardia, Ventricular - etiology; Ventricular Function
• DOI: 10.1002/j.1552-4604.1994.tb03984.x
• ISSN: 0091-2700

To evaluate the effects of programmed ventricular stimulation on resultant plasma concentrations of intravenously administered procainamide, drug dosing was performed with and without ventricular stimulation on two separate days (48 hours apart) in 12 dogs (13 dosing trials) at > or = 14 days after myocardial infarction (mean: 62 days). During infarct surgery, three bipolar electrodes were plunged into left ventricular epicardium, externalized, and later used for ventricular stimulation. On the first study day, procainamide was dosed to achieve two sequential plateau plasma levels (I and II), with a 20-minute equilibrium period at each plateau before ventricular stimulation. Plasma procainamide concentrations were measured before initiation of ventricular stimulation and at the completion of ventricular stimulation for each sequential plateau level. Stimulation involved delivery of one, two, and three extrastimuli at three paced cycle lengths at three left ventricular sites before procainamide dosing and at each of the two procainamide plateau levels. Three dogs were excluded from analysis due to induction of lethal ventricular arrhythmias. No ventricular arrhythmias were induced in the remaining nine animals. On the second study day, procainamide was dosed identically, but no ventricular stimulation was performed. Intravenous drug administration and collection of plasma concentration samples were performed with +/- 1 minute on both study days. Mean plasma procainamide concentrations at the end of ventricular stimulation at dosage Levels I & II were 10% and 12% greater (P < 0.02 and P < 0.005, respectively) than plasma concentrations measured at comparable times on the study day when no ventricular stimulation was performed.