Estimation of the probability for exceeding thresholds of urine specific gravity and plasma concentration of furosemide at various intervals after intravenous administration of furosemide in horses.
Abstract: To estimate the probability of concurrently exceeding thresholds for plasma concentration of furosemide and urine specific gravity after IV administration of furosemide in horses. Methods: 12 mature healthy Thoroughbred (n = 6) or Quarter Horse (6) mares. Methods: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after IV administration of 250 mg (first experiment) or 500 mg (second experiment) of furosemide. Urine was collected hourly between 1 and 6 hours after administration of furosemide at both doses. Concentrations of furosemide were determined by use of an ELISA. Concentration of furosemide and urine specific gravity was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic and specific gravity data, the probability of exceeding a concentration of 100 ng of furosemide/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess the inherent variation in this estimated probability. Results: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml and urine specific gravity < 1.012 was approximately 0% between 4.0 and 5.5 hours after IV administration of 250 mg of furosemide/horse, and ranged from 0 to 1% between 4 and 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified as in violation of regulatory concentrations was inversely associated with time. Conclusions: Coupling plasma furosemide concentration with urine specific gravity testing will greatly reduce the chance that some horses are misclassified as being in violation of regulatory concentrations.
Publication Date: 2001-09-19 PubMed ID: 11560258DOI: 10.2460/ajvr.2001.62.1349Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study investigates how the intrusion of a diuretic substance called furosemide, a drug commonly used to prevent bleeding in horses’ lungs during strenuous exercises, affects urine density and its plasma concentration in the horse’s body. The research’s main aim is to estimate the probability of exceeding thresholds for furosemide concentration and urine density following its intravenous administration in horses.
Research Methodology
- The subject group for this study comprised 12 mature and healthy female Thoroughbred and Quarter Horse horses.
- Each horse was injected intravenously with furosemide of specific doses (250 mg in the first experiment and 500 mg in the second experiment).
- Several measurements were taken both before and after the administration of the drug. Venous blood was collected at several intervals to keep track of any changes over time.
- Urine samples were taken every hour after administration between hour 1 and hour 6. The aim was to understand the effects of furosemide on urine concentration and horse plasma over time.
- The researchers measured furosemide concentrations through an ELISA (Enzyme-linked Immunosorbent Assay), a plate-based assay technique designed for detecting and quantifying substances.
- They then produced models of urine density and furosemide plasma concentration as a function of time, which included variations both between different horses and within the same horse.
Results of the Research
- The researchers found that the probability of exceeding the threshold for furosemide concentration and urine density was almost zero between 4 and 5.5 hours after a 250 mg dose.
- For a larger 500 mg dose, the probability ranged from 0% to 1% in the same time frame.
- It was observed that the likelihood of falsely identifying a horse as having violated regulatory concentrations was inversely proportionate to time.
Conclusion of the Study
- The study concludes that combining tests for plasma furosemide concentration with urine density tests can significantly reduce the chances of incorrectly identifying horses as violating regulatory concentrations.
- This could be particularly useful in a competitive sporting context, where horses might be unfairly disqualified based on misclassification of drug use.
Cite This Article
APA
Chu KK, Cohen ND, Stanley SD, Wang N.
(2001).
Estimation of the probability for exceeding thresholds of urine specific gravity and plasma concentration of furosemide at various intervals after intravenous administration of furosemide in horses.
Am J Vet Res, 62(9), 1349-1353.
https://doi.org/10.2460/ajvr.2001.62.1349 Publication
Researcher Affiliations
- Department of Statistics, College of Science, Texas A&M University, College Station 77843-4475, USA.
MeSH Terms
- Animals
- Diuretics / blood
- Diuretics / pharmacokinetics
- Diuretics / urine
- False Positive Reactions
- Female
- Furosemide / blood
- Furosemide / pharmacokinetics
- Furosemide / urine
- Horses / blood
- Horses / metabolism
- Horses / urine
- Injections, Intravenous / veterinary
- Regression Analysis
- Specific Gravity / drug effects
- Urine / chemistry
Grant Funding
- R01 CA074552 / NCI NIH HHS
- R01 CA074552-06 / NCI NIH HHS
Citations
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