Detection, quantification, and pharmacokinetics of furosemide and its effects on urinary specific gravity following IV administration to horses.

This study explores the effects of the diuretic Furosemide on horses, its pharmacokinetics, and how it can interfere with the detection of other substances. The researchers have devised a method to track the drug in horses’ bodies and determine its effects on urinary specific gravity.

Furosemide in equine racing

• Furosemide is a potent diuretic often used in horses to prevent exercise-induced pulmonary hemorrhage, a health condition that can occur during intense physical exertion such as that seen in competitive horse racing.
• As furosemide can artificially lower the concentrations of other substances in horse urine, it could potentially be used to mask the use of performance-enhancing drugs. Therefore, its use is strictly controlled in horse racing.
• Regulations in many racing jurisdictions require paired limits of urinary specific gravity (less than 1.010) and serum concentrations of furosemide (above 100 ng/ml).

Research methodology

• The researchers developed a liquid chromatography/mass spectrometry/mass spectrometry method to track furosemide levels in horses. This method employs a solid-phase extraction procedure and uses furosemide-d5, a slightly different form of furosemide, as a standard of comparison.
• This method was used to study how furosemide behaved within horse bodies (its pharmacokinetics) and to assess its effects on urinary specific gravity following its administration (250 mg) to ten horses.

Findings of the study

• The study found that the distribution and elimination of furosemide in the horse’s body could adequately be described by a two-compartmental open model. In this model, the drug first spreads rapidly in the readily accessible ‘central’ compartment (like the bloodstream) and is then more slowly distributed to a ‘peripheral’ compartment (like fatty tissue or muscles).
• They also found that it’s unlikely for horses to have serum concentrations of furosemide greater than 100 ng/ml or urine specific gravity less than 1.010, 4 hours after the administration of a 250 mg dose. This result supports the current paired limit regulations.
• However, urinary specific gravity is highly variable in horses, and some may naturally exhibit low values even without furosemide administration, making it a less reliable parameter for the detection of potential drug masking.