Preliminary pharmacokinetics and cardiovascular effects of fenoldopam continuous rate infusion in six healthy dogs

Abstract

Fenoldopam is a selective dopamine-1 receptor agonist that causes peripheral arterial vasodilation, increased renal blood flow, and diuresis. Enthusiasm exists for the use of fenoldopam in non-polyuric kidney injury in dogs, though pharmacokinetic data is lacking. The purpose of this study was to collect basic pharmacokinetic and hemodynamic effect data for fenoldopam when administered to healthy awake dogs. Six healthy, awake beagles were given a 180 minute fenoldopam constant rate infusion at 0.8 μg/kg/min followed by a 120 minute washout period. Citrated blood was collected during and after infusion for plasma fenoldopam concentration measurement by HPLC with mass spectrometry. Heart rate and indirect systolic blood pressure were concurrently measured. Mean +/− SD steady state plasma fenoldopam concentrations of 20 +/− 17 ng/mL were achieved within 10 min of starting the infusion. Area under the plasma concentration-time curve was 3678 +/− 3030 ng/mL*min and plasma clearance was 66 +/− 43 mL/min/kg. Elimination was rapidly achieved in all dogs. Heart rate and systolic blood pressure were unaffected by the fenoldopam infusion. Based on the results of this study, further evaluation of the effects of fenoldopam in dogs at differing doses and in dogs with clinical conditions such as acute non-polyuric kidney injury is warranted.

Effect of Fenoldopam Continuous Infusion on Glomerular Filtration Rate and Fractional Excretion of Sodium in Healthy Dogs

“…If no hypotension was observed, the dosage was increased by 0.2 μg/kg/min increments every 5 minutes until reaching the desired dosage of 0.8 μg/kg/min. This target dosage was chosen based on previous pharmacokinetic studies performed using fenoldopam in dogs . This dosage necessitated a fluid administration rate of 1.2 mL/kg/h.…”

“…Blood pressure was measured before each dose increment to monitor for hypotension. Once the patient had received 0.8 μg/kg/min or the highest tolerated dosage of fenoldopam for 10 minutes, they were considered to have reached steady state . Once at steady state, dogs received the infusion for a total of 300 minutes in order to allow 60 minutes at steady state before performing the 240‐minute iohexol clearance test.…”

“…The most important adverse effect of fenoldopam infusion is hypotension, which appears to be dose dependent. Pharmacokinetic studies in dogs are limited, but a recent veterinary study of 6 healthy dogs demonstrated that steady‐state plasma concentrations were reached within 10 minutes of fenoldopam infusion (0.8 μg/kg/min), with no observed hypotension …”

Postoperative Management of Dogs With Gastric Dilatation and Volvulus

“…Fenoldopam pharmacokinetics has been evaluated in dogs. 36 Recently, we have had promising results with the use of fenoldopam in dogs with heatstroke, with treated dogs demonstrating increased GFR compared with the placebo group.…”

Peritoneal dialysis in acute renal failure in canines: A review

“…The three-layered peritoneal membrane minerals, anions, cations, certain drugs and toxins, and consists of 1) the mesothelium, a continuous monolayer excess fluid from the bloodstream. The extracorporeal of flat cells, and their basement membranes; 2) a very dialyzer distinguishes hemodialysis from peritoneal compliant interstitium; and 3) the capillary wall, dialysis, which uses a patient's peritoneum as the consisting of a continuous layer of mainly non-dialysis membrane (Bloom and Labato, 2011). fenestrated endothelial cells, supported by a basement…”