Fenoldopam

Selective D1-like dopamine receptor partial agonist (EC50 = 57 nM). Vasodilator in vivo and does not readily cross the blood-brain barrier. Also α2-adrenoceptor antagonist in vitro (Ki = 15 - 25 nM).

Effect of Fenoldopam Continuous Infusion on Glomerular Filtration Rate and Fractional Excretion of Sodium in Healthy Dogs.[Pubmed:27452198]

J Vet Intern Med. 2016 Sep;30(5):1655-1660.

BACKGROUND: Acute kidney injury (AKI) is a common problem in small-animal patients and carries a guarded prognosis with substantial morbidity and mortality, particularly in oligoanuric dogs. Fenoldopam, a selective dopamine agonist, has been shown to increase urine output in healthy dogs and cats; however, the mechanism of action is unknown. HYPOTHESIS/OBJECTIVES: To evaluate the effect of Fenoldopam infusion on glomerular filtration rate (GFR) and fractional excretion of sodium (FeNa) in healthy dogs. ANIMALS: Ten healthy, privately owned dogs. METHODS: Randomized, crossover design with negative control. Ten healthy dogs were given Fenoldopam diluted in 5% dextrose (D5W) as a continuous IV infusion of 0.8 mug/kg/min for 5 hours and a control infusion of D5W alone, 7 days apart. Glomerular filtration rate was measured by exogenous iohexol clearance, beginning 1 hour after the start of the Fenoldopam infusion. Fractional excretion of sodium (FeNa) was measured before and after the infusion. Glomerular filtration rate and change in FeNa were compared between treatment days. RESULTS: Fenoldopam infusion resulted in a significantly increased (P = .0166) GFR (median GFR, 3.33 mL/min/kg) in healthy dogs compared with D5W infusion (median GFR, 2.71 mL/kg/min). Fenoldopam also resulted in a significantly increased (P = .0148) FeNa (mean change, 0.106), whereas infusion of D5W alone did not (mean change, 0.016). CONCLUSIONS AND CLINICAL IMPORTANCE: In healthy dogs, Fenoldopam significantly increased GFR and FeNa compared with infusion of D5W alone. No adverse effects were seen.

Fenoldopam to prevent acute kidney injury after major surgery-a systematic review and meta-analysis.[Pubmed:26703329]

Crit Care. 2015 Dec 25;19:449.

BACKGROUND: Acute kidney injury (AKI) after surgery is associated with increased mortality and healthcare costs. Fenoldopam is a selective dopamine-1 receptor agonist with renoprotective properties. We conducted a systematic review and meta-analysis of randomised controlled trials comparing Fenoldopam with placebo to prevent AKI after major surgery. METHODS: We searched EMBASE, PubMed, meta-Register of randomised controlled trials and Cochrane CENTRAL databases for trials comparing Fenoldopam with placebo in patients undergoing major surgery. The primary outcome was incidence of new AKI. Secondary outcomes were requirement for renal replacement therapy and hospital mortality. RESULTS: Eighty-three publications were screened; 23 studies underwent full data extraction and scoring. Six trials were suitable for inclusion in the data synthesis (total of 507 subjects undergoing cardiovascular surgery, partial nephrectomy, liver transplant surgery). Five studies were rated at high risk of bias. Data on post-operative incidence of AKI were available in five of the six trials (total of 471 patients) but definitions of AKI varied between studies. Of the 238 patients receiving Fenoldopam, 45 (18.9%) developed AKI compared to 62 (26.6%) of the 233 patients who received placebo (p = 0.004, I (2) = 0 %; random-effects model odds ratio 0.46, 95% confidence interval 0.27-0.79). In patients treated with Fenoldopam, there was no difference in renal replacement therapy (n = 478; p = 0.11, I (2) = 47%; fixed-effect model odds ratio 0.27, 95% confidence interval 0.06-1.19) or hospital mortality (p = 0.60, I (2) = 0 %; fixed-effect model odds ratio 1.0, 95% confidence interval 0.14-7.37). CONCLUSIONS: In this analysis, peri-operative treatment with Fenoldopam was associated with a significant reduction in post-operative AKI but it had no impact on renal replacement therapy or hospital mortality. Equipoise remains for further large trials in this area since the studies were conducted in three types of surgery, the majority of studies were rated at high risk of bias and the criteria for AKI varied between trials.

The pharmacokinetics of intravenous fenoldopam in healthy, awake cats.[Pubmed:26763106]

J Vet Pharmacol Ther. 2016 Apr;39(2):202-4.

Fenoldopam is a selective dopamine-1 receptor agonist that improves diuresis by increasing renal blood flow and perfusion and causing peripheral vasodilation. Fenoldopam has been shown to induce diuresis and be well-tolerated in healthy cats. It is used clinically in cats with oliguric kidney injury at doses extrapolated from human medicine and canine studies. The pharmacokinetics in healthy beagle dogs has been reported; however, pharmacokinetic data in cats are lacking. The goal of this study was to determine pharmacokinetic data for healthy, awake cats receiving an infusion of Fenoldopam. Six healthy, awake, client-owned cats aged 2-6 years old received a 120-min constant rate infusion of Fenoldopam at 0.8 mug/kg/min followed by a 20-min washout period. Ascorbate stabilized plasma samples were collected during and after the infusion for the measurement of Fenoldopam concentration by HPLC with mass spectrometry detection. This study showed that the geometric mean of the volume of distribution, clearance, and half-life (198 mL/kg, 46 mL/kg/min, and 3.0 mins) is similar to pharmacokinetic parameters for humans. No adverse events were noted. Fenoldopam at a constant rate infusion of 0.8 mug/kg per min was well tolerated in healthy cats. Based on the results, further evaluation of Fenoldopam in cats with kidney disease is recommended.

THE EFFECTS OF FENOLDOPAM ON RENAL FUNCTION AND METABOLISM IN AN OVINE MODEL OF SEPTIC SHOCK.[Pubmed:26506071]

Shock. 2016 Apr;45(4):385-92.

INTRODUCTION: The importance of renal perfusion and metabolism in septic acute kidney injury (AKI) remains unclear. Prophylactic administration of the dopaminergic agent, Fenoldopam, has been suggested to reduce the occurrence of AKI, but its effects in septic shock are poorly defined. METHODS: Sepsis was induced in 15 adult female sheep by injecting autologous feces into the abdominal cavity. Two hours later, the animals were randomized to one of three groups: low-dose Fenoldopam (1.0 mug/kg/min, n = 5), high-dose Fenoldopam (5.0 mug/kg/min, n = 5), or placebo (control, n = 5). A perivascular flow probe was placed around the renal artery and a catheter in the renal vein for measurement of renal blood flow index (RBFI) and oxygen consumption (VO2renI). Metabolism in the renal cortex was evaluated using microdialysis. Serum creatinine was measured 6-hourly and the sublingual microcirculation assessed using sidestream dark-field videomicroscopy. RESULTS: High-dose Fenoldopam was associated with a lower RBFI at 18 h (P = 0.032) than in the control group, but VO2renI was maintained by a higher oxygen extraction (P < 0.05 vs. baseline). Sublingual microcirculatory alterations at 18 h were more severe in the high-dose than in the control and low-dose groups (P = 0.021 and P = 0.032). Renal cortex lactate and pyruvate levels increased earlier in the high-dose group than in the other two groups (P < 0.001 vs. baseline). Fenoldopam did not affect creatinine clearance or urine output. CONCLUSIONS: In this model of septic shock, Fenoldopam did not improve renal blood flow, worsened microcirculatory alterations, and induced metabolic changes that were indicative of increased glycolysis.