The effect of oral fenoldopam (SKF 82526‐J), a peripheral dopamine receptor agonist, on blood pressure and renal function in normal man.

Abstract

1 The effect of a single oral dose of 100 mg of fenoldopam on renal function and blood pressure was investigated in seven healthy male subjects in a double-blind placebo controlled study. 2 Mean diastolic blood pressure fell by 10 mm Hg, 45 min after oral dosing and then gradually returned to baseline values. There was an increase in pulse rate and a delayed rise in systolic blood pressure. 3 Measured from 30 to 120 min after drug ingestion, mean effective renal plasma flow increased to 158% of the value observed after placebo; mean glomerular filtration rate rose to 109% of the placebo value. Measured from 120 to 210 min after administration of the drug, effective renal plasma flow and glomerular filtration rate had returned to baseline values. 4 Fenoldopam produced a small increase in the mean sodium excretion rate which was not significantly different from the fall after placebo. No change was detected in urine flow or potassium excretion rate. 5 Mean plasma renin activity increased three-fold 1 h after oral dosing. Plasma aldosterone did not show a parallel increase although the plasma concentration at 1 h was significantly higher than after placebo. 6 The results show a pronounced renal vasodilator effect lasting about 2 h. The findings are consistent with marked DA1 receptor agonist activity.Keywords fenoldopam (SKF 82526-J) dopamine renal blood flow blood pressure

Studies with fenoldopam, a dopamine receptor DA1 agonist, in essential hypertension.

“…The protocol for this section was identical to our studies with normal subjects (Harvey et al, 1985) but with the addition of urine uric acid determinations. Briefly, urine for measurement of volume, sodium, potassium and uric acid excretion was collected for 2 h before, and from 0-2 and 2-4 h after administration of drug or placebo.…”

“…(1972) which we described previously (Harvey et al, 1985). Isotope excreted in a given time period is divided by the area under the plasma concentration curve in that period.…”

Continuous intragastric delivery of fenoldopam: relationship between plasma concentration and effects on renal function.

“…The pharmacodynamic properties of fenoldopam have been studied following both intravenous and oral administration (Stote et al, 1983;Harvey et al, 1985). In particular, oral doses of up to 100 mg in healthy volunteers have been shown to produce significant, dose-related increases in renal plasma flow, urine flow rate, and free water clearance.…”

“…The development of this benzazepine derivative followed the elucidation of the role of dopamine in the regulation of vascular tone and blood pressure (Stoof & Kebabian, 1984;Yeh et al, 1969; Leenders et al, 1984;Langer, 1974 it does not produce such effects in the intact animal because of poor penetration across the blood-brain barrier (Harvey et al, 1985).…”

Haemodynamic and pharmacokinetic study of intravenous fenoldopam in patients with hepatic cirrhosis.

“…Fenoldopam is a benzazepine derivative with post-synaptic dopaminergic receptor agonist action which unlike dopamine lacks significant a-or 3-adrenoceptor activity (Hahn et al, 1982;Harvey et al, 1985;Ohlstein et al, 1984;Stote et al, 1983). Oral administration of fenoldopam is followed by rapid absorption and an extensive first pass metabolism by the liver (Cyronac et al, 1987).…”