The pharmacokinetics of furosemide in anaesthetized horses after bilateral ureteral ligation.

This study investigates the behavior of the drug furosemide in anaesthetized horses, specifically under conditions of bilateral ureteral ligation (BUL). The research further evaluates any potential impacts of premedication with the drug phenylbutazone on the furosemide’s pharmacokinetics.

Experiment Design

• The researchers administered furosemide, a commonly used diuretic, to two groups of anaesthetized horses. In one group (5 horses), the horses underwent BUL – the literal blocking off of the horses’ ureters, the tubes that carry urine from kidneys to the bladder. The second group (also 5 horses) did not undertake BUL.
• The study also examined the effect of another medication, phenylbutazone – a painkiller and anti-inflammatory, on furosemide pharmacokinetics by administering it prior to furosemide.
• Following furosemide administration, plasma samples were collected for up to 3 hours and analysed using high performance liquid chromatography method, a common method to separate, identify and quantify each component in a mixture.

Results and Interpretation

• The analysis measured different pharmacokinetic parameters: median plasma clearance of furosemide, apparent steady state volume of distribution and the elimination half-life.
• In the BUL horses, the median plasma clearance rate of furosemide was determined to be 1.4 mL/min/kg. This rate indicates the volume of plasma from which the drug is completely removed per unit time.
• The apparent steady state volume of distribution ranged from 169 to 880 mL/kg, reflecting the extent of the drug distribution in the body. Elimination half-life, the time required to decrease the drug concentration by half, spanned from 83 minutes to 209 hours.
• In this study, no differences in plasma concentration or kinetic parameter estimates were observed when phenylbutazone was administered prior to furosemide.
• The team concluded that BUL significantly reduces the elimination of furosemide in horses, thus confirming that extreme changes in kidney function can significantly impact drug kinetics in horses.

The research provides valuable insights into how severe kidney impairment may influence drug behavior in horses, a factor that veterinarians need to consider in their practice regarding drug administration and dosage.