A new oral renal vasodilator, fenoldopam

Abstract

Fenoldopam, a dopamine agonist, was evaluated in renal clearance studies during water diuresis after oral doses of 25, 50, and 100 mg. After the 100-mg dose there was an increase in urine flow rate, paraaminohippurate clearance, free water clearance, and an increase in the fractional excretion of sodium, calcium, and uric acid. These effects were evident within the first hour, peaked during the second hour, and lasted about 3 hr. Doses of 50 and 25 mg induced smaller increases. There was no significant change in inulin clearance at any dose. To elucidate the mechanism of action, the studies were repeated after treatment with a dopamine-receptor antagonist (metoclopramide). Metoclopramide greatly diminished the renal effects of fenoldopam. These findings indicate that fenoldopam is an active renal vasodilator in man and increases urine volume, free water clearance, and fractional excretion of sodium by stimulation of renal dopamine receptors.

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

“…As a result of the increase in RPF and the unchanged GFR in this study, there is a decrease in the fraction GFR/RPF. As discussed by Stote et al (1983), this fall in filtration fraction results in decreased reabsorption of proximal tubular fluid and increased delivery out of the proximal tubule. In the present study as well as in this earlier work, increased delivery from the proximal tubule is associated with a mild natriuresis, the mechanism of which remains unclear.…”

“…In the present study as well as in this earlier work, increased delivery from the proximal tubule is associated with a mild natriuresis, the mechanism of which remains unclear. Potential explanations include volume expansion associated with the inhibition of sodium reabsorption in the distal tubule, washout of the medullary concentration gradient, or direct pharmacologic effects of fenoldopam (Stote et al, 1983).…”

“…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.…”

“…Fenoldopam, a potent agonist at peripheral dopamine1 (DA1)-receptors, has been shown to produce beneficial haemodynamic effects including an improvement in renal plasma flow and a reduction in blood pressure following both intravenous and oral administration (Stote et al, 1983;Ventura et al, 1984). 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).…”