Pharmacokinetic and pharmacodynamic properties of intravenous fenoldopam, a dopamine1‐receptor agonist, in hypertensive patients.

Rr, Weber; McCoy, C. E.; Ziemniak, JA; Frederickson, E D; Li, Goldberg; Murphy, Michael B.

doi:10.1111/j.1365-2125.1988.tb03276.x

Cited by 62 publications

(35 citation statements)

References 7 publications

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“…The oral administration of fenoldopam to normal and hypertensive subjects as well as i. v. infusion to experimental animals and men clearly demonstrate a dose-dependent decrease in blood pressure, an increase in renal blood flow, and in most instances an increase in sodium excretion at lower doses [Hahn et al, 1982;Ventura et al, 1984;Harvey et al, 1986;Murphy 66 Dlewati and Lokhandwala Jose et al, 1987;Weber et al, 1988;White et al, 1988;Hegde et al, 19891. In hypertensive subjects the average infusion rate needed to decrease diastolic and mean blood pressure ranges from 0.25 to 0.5 pg/kg/min [Weber et al, 19881.…”

Section: Discussionmentioning

confidence: 99%

Dose‐response analysis of the effects of fenoldopam, dopamine‐1 receptor agonist, on renal function

Dlewati

Lokhandwala

1991

Drug Development Research

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The present study was carried out to perform a dose-response analysis of the effect of fenoldopam, a DA-1 receptor agonist, on renal sodium excretion. Infusions of fenoldopam for 30 min at doses of 0.125, 0.25, 0.5, and 1.0 pg/kg/min in four separate groups of pentobarbital-anesthetized dogs caused dose-dependent hypotension and renal vasodilation. The reflex tachycardic response was not dose-dependent and seen only with the three higher doses. There was no change in glomerular filtration with any of the four doses of fenoldopam. At the doses of 0.25 and 0.5 pg/kg/min fenoldopam caused significant increases in urine volume, urinary sodium excretion, and fractional excretion of sodium during the infusion as well as during the first recovery period of 30 min. At the highest dose of 1 pg/kg/min no diuresis or natriuresis was seen during the infusion: however, significant increases in urine volume and sodium excretion were seen during the two recovery periods. At the lowest dose (0.125 pg/kg/min) fenoldopam caused minimal hemodynamic changes but produced maximum increases in urine volume and urinary sodium excretion. These effects of fenoldopam were antagonized by the DA-I receptor antagonist, SCH 23390. The results of our study show that the tubular effects of fenoldopam leading to increased renal sodium excretion are evident at doses lower than those required to cause changes in systemic and renal hemodynamics. In addition, at higher doses when the magnitude of hypotension is very pronounced, this effect may limit the increase in sodium excretion produced by fenoldopam.

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Section: Discussionmentioning

confidence: 99%

Dose‐response analysis of the effects of fenoldopam, dopamine‐1 receptor agonist, on renal function

Dlewati

Lokhandwala

1991

Drug Development Research

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“…Fen is FDA-approved to treat renal hypertension, 18 while causing only a small drop in blood pressure in normotensive patients. 19 Given its short half-life in the circulation, 20 Fen is commonly administered by infusion.…”

Section: Introductionmentioning

confidence: 99%

Expression and therapeutic targeting of dopamine receptor-1 (D1R) in breast cancer

et al. 2015

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Patients with advanced breast cancer often fail to respond to treatment, creating a need to develop novel biomarkers and effective therapeutics. Dopamine (DA) is a catecholamine which binds to five G-protein-coupled receptors. We discovered expression of DA type-1 receptors (D1R) in breast cancer, thereby identifying these receptors as novel therapeutic targets in this disease. Strong to moderate immunoreactive D1R expression was found in 30% of 751 primary breast carcinomas, and was associated with larger tumors, higher tumor grades, node metastasis, and shorter patient survival. DA and D1R agonists, signaling through the cGMP/protein kinase G (PKG) pathway, suppressed cell viability, inhibited invasion, and induced apoptosis in multiple breast cancer cell lines. Fenoldopam, a peripheral D1R agonist which does not penetrate the brain, dramatically suppressed tumor growth in two mouse models with D1R-expressing xenografts by increasing both necrosis and apoptosis. D1R-expressing primary tumors and metastases in mice were detected by fluorescence imaging. In conclusion, D1R overexpression is associated with advanced breast cancer and poor prognosis. Activation of the D1R/cGMP/PKG pathway induces apoptosis in vitro and causes tumor shrinkage in vivo. Fenoldopam, which is FDA-approved to treat renal hypertension, could be repurposed as a novel therapeutic agent for patients with D1R-expressing tumors.

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“…Fenoldopam is rapidly titratable, with an elimination half-life of less than 10 minutes. 85 Fenoldopam has primarily been used in adults for the shortterm treatment of severe hypertension. 86 Some studies have demonstrated favorable hemodynamic responses in adults with New York Heart Association class III-IV heart failure, including improved cardiac index and lower systemic vascular resistance and left ventricular filling pressure.…”

Section: Fenoldopammentioning

confidence: 99%

Acute Kidney Injury and Critical Cardiac Disease

Cooper

Charpie

Flores

et al. 2011

World J Pediatr Congenit Heart Surg

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The field of cardiac intensive care continues to advance in tandem with congenital heart surgery. The survival of patients with critical congenital heart disease is seldom in question. Consequently, the focus has now shifted to that of morbidity reduction and eventual elimination. Acute kidney injury (AKI) after cardiac surgery is associated with adverse outcomes, including prolonged intensive care and hospital stays, diminished quality of life, and increased long-term mortality. Acute kidney injury occurs frequently, complicating 30% to 40% of adult and pediatric cardiac surgeries. Patients who require dialysis are at high risk of mortality, but even minor degrees of postoperative AKI portend a significant increase in mortality and morbidity.

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Pharmacokinetic and pharmacodynamic properties of intravenous fenoldopam, a dopamine1‐receptor agonist, in hypertensive patients.

Cited by 62 publications

References 7 publications

Dose‐response analysis of the effects of fenoldopam, dopamine‐1 receptor agonist, on renal function

Dose‐response analysis of the effects of fenoldopam, dopamine‐1 receptor agonist, on renal function

Expression and therapeutic targeting of dopamine receptor-1 (D1R) in breast cancer

Acute Kidney Injury and Critical Cardiac Disease

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