Thirty-three patients with mild-to-moderate
essential hypertension received either placebo or
fenoldopam, a selective dopamine-1 agonist, by
intravenous infusion at a fixed infusion rate ranging from 0.1 to 0.8 microg/kg/min for 48 h during a double-blind, placebo-controlled, randomized inpatient clinical trial. Blood pressure and heart rate were measured every 15 min for 24 h before, during, and 24 h after the 48-h
drug infusion. Plasma concentrations of racemic
fenoldopam were measured at frequent intervals during and for 24 h after
fenoldopam infusion. In the 26 patients who received
fenoldopam, there were dose-dependent reductions in systolic and diastolic blood pressure, which usually reached a nadir within 2 h of beginning infusion and were significant even at the lowest dose studied (-9 and -9 mm Hg for systolic and diastolic blood pressure, respectively, at 24 h for the dose of 0.04 microg/kg/min, P < .05). There were associated increases in heart rate that were greater in the first than in the last 24 h of
drug infusion. Compared to the average 24-h control blood pressure, maximum mean reductions in systolic and diastolic blood pressures of 33 and 21 mm Hg, respectively, were noted in patients receiving
fenoldopam at 0.8 microg/kg/min and occurred 4 and 1 h, respectively, after beginning infusion. Tolerance to the blood pressure lowering effects of the
drug developed slowly during the 48 h of
drug infusion; the half-life for this effect was 60 h. No serious adverse clinical effects were noted in any patient. These results demonstrate that
fenoldopam is effective in reducing blood pressure of patients with mild-to-moderate
hypertension at doses as low as 0.04 microg/kg/min, is well tolerated at doses up to 0.8 microg/kg/min, maintains most of its
antihypertensive efficacy throughout 48 h of continuous, constant rate infusion, and produces neither prolonged pharmacodynamic effects nor rebound
hypertension when discontinued. The pharmacodynamic effects of the
drug are best predicted by pharmacokinetics of racemic and R-
fenoldopam.