Serum drug concentrations and adverse effects in cardiac patients after administration of a new controlled-release disopyramide preparation.

Despite widespread marketing of a controlled-released preparation of disopyramide phosphate (Norpace-CR, G. D. Searle), literature demonstrating its efficacy in maintaining uniform serum drug levels over a 12-h dosing interval is derived from only normal healthy volunteers. Twenty patients with cardiac arrhythmias (ages 37-80 years) were administered 400-800 mg/24 h (5.1-10.5 mg/kg/day) of controlled-release disopyramide in two equally divided doses on a q. 12 h. schedule. After achievement of steady-state equilibrium drug concentration, disopyramide levels were determined by high-pressure liquid chromatography on sera obtained from blood samples drawn 2, 7, and 11 h after an oral dose. Mean maximal and minimal disopyramide serum concentrations were 3.2 +/- 1.0 and 2.5 +/- 0.9 microgram/ml, respectively. Adverse drug effects occurred in nine (45%) subjects, necessitating discontinuation of the preparation in five patients (25%). These data demonstrate that in a population of patients with cardiac arrhythmias q. 12 h. dosing with a controlled-release disopyramide phosphate preparation is associated with an acceptable variation between maximal and minimal serum disopyramide concentrations, and is tolerated by the majority of subjects. The preparation should, therefore, offer greater patient convenience and compliance without sacrificing antiarrhythmic efficacy.