SYSTEMIC DELIVERY OF SYMPATHOMIMETIC AMINES BY TRANSDERMAL IONTOPHORESIS

Certain sympathomimetic amines may be useful in the treatment or diagnosis of cardiovascular disease. However, obtaining sufficient blood levels of these drugs when given orally is difficult because of gastrointestinal destruction and their is a danger associated with intravenous administration. These problems have prompted the investigation of iontophoretic delivery of a novel sympathomimetic amine, KM-13, across the skin of anesthetized dogs. Dogs were monitored to determine cardiac rate or cardiac contractility. The KM-13 was dissolved in distilled H2O to a concentration of 50 mM and placed in a 15 cm(2) matrix pad beneath the positive electrode of a DC constant current device. Delivered currents of 0.5-4.0 mA caused graded increases in cardiac contraction which reached a plateau within 20-30 min. In other dogs, delivery of 1 mA current for 15 min caused an increase in heart rate which peaked at about 24 min and decayed with a T-1/2 of approx. 95 min. Prior treatment of skin beneath the positive electrode pad with tolazoline (an alpha-adrenergic blocker) caused a more rapid response (peak with 15 min) and decay (T-1/2 of approx. 51 min) to KM-13. This study demonstrates that iontophoretic delivery of a sympathomimetic amine is feasible. Prolonged latency of onset and decay may cause problems in same uses. Prior use of vasodilators before applications of sympathomimetic amines can accelerate onset and decay.