Long-term intravenous infusion of antiarrhythmic drugs using a totally implanted drug delivery system

Abstract

In vitro and in vivo testing was performed to establish the feasibility of a totally implantable pump system to deliver antiarrhythmic agents. In vitro flow characteristics suggested predictable day to day delivery with acceptably small variations in flow with changes in reservoir volume or temperature. During 3 months of in vitro testing, procainamide and bretylium were found suitable for long-term delivery. Delivery of lidocaine was limited by high viscosity and corrosion of steel elements within the pump. The pump was implanted in a subcutaneous pocket in four dogs. Procainamide (0.5 g/ml), delivered at 4 ml/day (70 mg/kg body weight per day), provided a mean steady state drug concentration of 5.3 [mu]g/ml. Bretylium (50 mg/ml), delivered at 8 ml/day (13 mg/kg per day), provided a steady state concentration of 0.8 [mu]g/ml (range 0.4 to 1.4). Long-term intravenous administration of therapeutic doses of bretylium and procainamide with this delivery system has been demonstrated in dogs and appears to be feasible in human subjects.