Copyright © 2008 Hammer et al; licensee BioMed Central Ltd.
Pharmacokinetics and pharmacodynamics of fenoldopam mesylate for blood pressure control in pediatric patients
1Departments of Anesthesia and Pediatrics, Stanford University School of Medicine, Stanford, USA
2Departments of Anesthesia and Pediatrics, Children's National Medical Center, George Washington University School of Medicine, Washington, USA
3Department of Anesthesia, Stanford University School of Medicine, Stanford, USA
4Departments of Anesthesiology, Critical Care Medicine, and Pediatrics, Johns Hopkins University, Baltimore, USA
5Departments of Anesthesiology and Pediatrics, Wake Forest University School of Medicine, Winston-Salem, USA
Gregory B Hammer: email@example.com; Susan T Verghese: firstname.lastname@example.org; David R Drover:email@example.com; Myron Yaster: firstname.lastname@example.org; Joseph R Tobin: email@example.com
Received April 7, 2008; Accepted October 6, 2008.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Fenoldopam mesylate, a selective dopamine1-receptor agonist, is used by intravenous infusion to treat hypertension in adults. Fenoldopam is not approved by the FDA for use in children; reports describing its use in pediatrics are limited. In a multi-institutional, placebo controlled, double-blind, multi-dose trial we determined the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and side-effect profile of fenoldopam in children.
Seventy seven (77) children from 3 weeks to 12 years of age scheduled for surgery in which deliberate hypotension would be induced were enrolled. Patients were randomly assigned to one of five, blinded treatment groups (placebo or fenoldopam 0.05, 0.2, 0.8, or 3.2 mcg/kg/min iv) for a 30-minute interval after stabilization of anesthesia and placement of vascular catheters. Following the 30-minute blinded interval, investigators adjusted the fenoldopam dose to achieve a target mean arterial pressure in the open-label period until deliberate hypotension was no longer indicated (e.g., muscle-layer closure). Mean arterial pressure and heart rate were continuously monitored and were the primary endpoints.
Seventy-six children completed the trial. Fenoldopam at doses of 0.8 and 3.2 mcg/kg/min significantly reduced blood pressure (p < 0.05) during the blinded interval, and doses of 1.0–1.2 mcg/kg/min resulted in continued control of blood pressure during the open-label interval. Doses greater than 1.2 mcg/kg/min during the open-label period resulted in increasing heart rate without additional reduction in blood pressure. Fenoldopam was well-tolerated; side effects occurred in a minority of patients. The PK/PD relationship of fenoldopam in children was determined.
Fenoldopam is a rapid-acting, effective agent for intravenous control of blood pressure in children. The effective dose range is significantly higher in children undergoing anesthesia and surgery (0.8–1.2 mcg/kg/min) than as labeled for adults (0.05–0.3 mcg/kg/min). The PK and side-effect profiles for children and adults are similar