RENAL AND SYSTEMIC HEMODYNAMIC EFFECTS OF VERY-LOW DOSE FENOLDOPAM IN NORMOTENSIVE SUBJECTS

Abstract

Introduction. Fenoldopam (Corlopam[registered sign], Neurex Division of Elan Pharmaceuticals) is a newly approved, short-acting, specific dopamine receptor (DA-1) agonist that dilates systemic, renal, splanchnic, and coronary vascular beds. Methods. To determine the dose ranges over which renal vasodilation occurs without blood pressure (BP) lowering in individuals who are normotensive, we studied 13 normotensive subjects in sodium balance at 300 meq/day in a double-blinded, crossover, placebo-controlled trial. Fenoldopam doses of 0.001 to 0.2 [micro sign]g/kg/min were given in a fixed sequential, escalating manner for 30 minutes each by continuous infusion. Renal plasma flow, a marker of renal blood flow, was measured using para-aminohippurate (PAH) clearance. Data is expressed as means +/- SEM. Statistical significance (*) is defined as P <or=to 0.05. Results. The subjects were all male (10 Caucasian, 3 Black) with a mean age of 31.6 +/- 2.1 years and mean baseline SBP of 123.0 +/- 3.4 and DBP of 80.5 +/- 2.7 mmHg. Fenoldopam, but not placebo increased renal blood flow in a dose-dependent manner, starting at doses as low as 0.01 [micro sign]g/kg/min (see Figure 1). Furthermore, increases in renal blood flow persisted for at least two hours following drug discontinuation. There were no changes in glomerular filtration rate as measured by inulin clearance. Mean changes in SBP and DBP compared with baseline are shown in Table 1 below. Unlike the renal effects, the blood pressure effects disappeared rapidly and were indiscernible by the first measurement of blood pressure following drug discontinuation (30 minutes), consistent with prior pharmacodynamic studies.Figure 1: Change in Renal Blood Flow vs Fenoldopam DoseTable 1Discussion. These results expand the known renal dose-response curve of fenoldopam and confirm the lack of significant lowering of BP in individuals who are initially normotensive at doses up to 0.1 [micro sign]g/kg/min. Differences in renal and systemic pharmacodynamics may be related to the differences in secondary messenger systems for systemic and renal DA-1 receptors. Normotensive patients can be safely treated with fenoldopam in situations in which increasing renal blood flow is desirable.