Pharmacokinetics of furosemide administered 4 and 24 hours prior to high-speed exercise in horses.

This research article investigates the effects and pharmacokinetics of the diuretic drug furosemide when it’s administered to Thoroughbred horses 4 and 24 hours prior to strenuous exercise on a high-speed treadmill.

Overview

The main aim of this study is to evaluate the pharmacokinetics, the manner how a drug is absorbed, distributed, metabolized, and excreted, of furosemide in a scenario where racehorses are subjected to high-intensity exercise. In racing, furosemide is frequently used to mitigate exercise-induced pulmonary hemorrhage (EIPH). This study tests how the timing of the administration of the drug could potentially influence its efficacy.

Methodology

• The study involved eight Thoroughbred horses, all of adult age, which underwent treatment with furosemide and then engaged in intense exercise.
• Horses were treated with a single intravenous (IV) administration of 250mg furosemide 4 hours and 24 hours prior to executing high-speed exercise on a treadmill.
• Various blood and urine samples were collected from the horses both before the exercise (time 0) and at regular intervals up to 72 hours afterward.
• The concentrations of furosemide in these samples were then determined using a method called liquid chromatography-tandem mass spectrometry.

Findings

• The concentration of serum furosemide remained above the limit of quantification (LOQ, the lowest amount of an analyte that can be sensibly measured by an analytical procedure) for 36 hours in 3 out of the 8 horses in the 4-hours group and 1 out of the 8 horses in the 24-hours group.
• The concentration data for the serum proved to best fit a two-compartment model, which is a model used in pharmacokinetics that describes the drug concentration in the body over time as it moves between two “compartments” — central (the bloodstream) and peripheral (outside the bloodstream).
• There was found to be no significant difference in the volume of distribution (how extensively a drug disperses throughout the body) at steady-state, or in the systemic clearance (the total body clearance of the drug from plasma) between horses that were exercised at 4- and 24-hours postdrug administration.
• The average elimination half-life (the time it takes for the body to reduce the concentration of the drug by half) was calculated to be apporximately 3.12 hours and 3.23 hours following administration 4 hours and 24 hours prior to exercise, respectively.

Conclusions

In summary, this study provides a detailed account of how the concentrations and characteristics of furosemide in serum and urine of Thoroughbred horses vary following its administration and subsequent high-intensity exercise. However, it suggests that the timing of the administration of furosemide (between 4 and 24 hours prior to exercise) does not significantly affect its distribution, metabolism, or excretion.