Prolonged fenoldopam infusions in patients with mild to moderate hypertension: Pharmacodynamic and pharmacokinetic effects

Addison A. Taylor, Alexander M. Shepherd, William Polvino, Roberto Mangoo-Karim, Kevin Ballard, Sarat Sunthornyothin, Robert R. Luther, James L. Pool

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Thirty-three patients with mild-to-moderate essential hypertension received either placebo or fenoldopam, a selective dopamine-1 agonist, by intravenous infusion at a fixed infusion rate ranging from 0.1 to 0.8 μg/kg/min for 48 h during a double-blind, placebo-controlled, randomized inpatient clinical trial. Blood pressure and heart rate were measured every 15 min for 24 h before, during, and 24 h after the 48-h drug infusion. Plasma concentrations of racemic fenoldopam were measured at frequent intervals during and for 24 h after fenoldopam infusion. In the 26 patients who received fenoldopam, there were dose-dependent reductions in systolic and diastolic blood pressure, which usually reached a nadir within 2 h of beginning infusion and were significant even at the lowest dose studied (-9 and -9 mm Hg for systolic and diastolic blood pressure, respectively, at 24 h for the dose of 0.04 μg/kg/min, P < .05). There were associated increases in heart rate that were greater in the first than in the last 24 h of drug infusion. Compared to the average 24-h control blood pressure, maximum mean reductions in systolic and diastolic blood pressures of 33 and 21 mm Hg, respectively, were noted in patients receiving fenoldopam at 0.8 μg/kg/min and occurred 4 and 1 h, respectively, after beginning infusion. Tolerance to the blood pressure lowering effects of the drug developed slowly during the 48 h of drug infusion; the half-life for this effect was 60 h. No serious adverse clinical effects were noted in any patient. These results demonstrate that fenoldopam is effective in reducing blood pressure of patients with mild-to-moderate hypertension at doses as low as 0.04 μg/kg/min, is well tolerated at doses up to 0.8 μg/kg/min, maintains most of its antihypertensive efficacy throughout 48 h of continuous, constant rate infusion, and produces neither prolonged pharmacodynamic effects nor rebound hypertension when discontinued. The pharmacodynamic effects of the drug are best predicted by pharmacokinetics of racemic and R-fenoldopam.

Original languageEnglish (US)
Pages (from-to)906-914
Number of pages9
JournalAmerican Journal of Hypertension
Volume12
Issue number9 I
DOIs
StatePublished - Sep 1999

Keywords

  • Fenoldopam
  • Hypertension
  • Pharmacodynamics
  • Pharmacokinetics

ASJC Scopus subject areas

  • Internal Medicine

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