Clinical development of dopexamine hydrochloride (Dopacard) and an overview of its hemodynamic effects.
A clinical development program was initiated to identify the hemodynamic profile of activity of dopexamine hydrochloride. Studies in healthy subjects confirmed the cardiovascular activity of dopexamine hydrochloride and demonstrated its potency. Doses of 0.5 to 8 micrograms/kg/min doubled cardiac output without change in mean blood pressure, although pulse pressure did widen. In patients with stable chronic cardiac failure (mainly New York Heart Association class III), dopexamine hydrochloride (4 micrograms/kg/min) increased stroke volume 47 +/- 9%, cardiac index 64 +/- 10% and heart rate 11.7 +/- 3%. Systemic vascular resistance decreased by 42 +/- 5%. At higher doses, cardiac index increased further, but chronotropic effects became more prominent. Subsequent studies in patients recovering from cardiac surgery and studies of longer duration in patients with chronic congestive heart failure have demonstrated a similar hemodynamic profile that is sustained throughout the infusion. The renal vasodilator effects have been confirmed in both healthy subjects and patients. With all catecholamines the balance of chronotropic to inotropic or vasodilator effect is critical. Dopexamine hydrochloride (1 to 4 micrograms/kg/min) increases cardiac index by over 40% at clinically insignificant (10%) increases of heart rate.