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American journal of veterinary research2001; 62(3); 320-325; doi: 10.2460/ajvr.2001.62.320

Estimation of the probability for exceeding a threshold concentration of furosemide at various intervals after intravenous administration in horses.

Abstract: To estimate the probability for exceeding a threshold concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses. Methods: 12 mature healthy horses (6 Thoroughbreds and 6 Quarter Horses). 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 administration of 250 or 500 mg of furosemide. Concentrations of furosemide were determined, using an ELISA. Concentration of furosemide was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic data, the probability for exceeding a concentration of 100 ng/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess inherent variation in this estimated probability. Results: The estimated probability of exceeding the threshold of 100 ng of furosemide/ml ranged from 11.6% at 4 hours to 2.2% at 5.5 hours after IV administration of 250 mg of furosemide/horse and 34.2% at 4 hours to 12.3% at 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified in violation of regulatory concentrations was inversely associated with time and positively associated with dose. Conclusions: Interhorse variability with respect to pharmacokinetics of furosemide will result in misclassification of some horses as being in violation of regulatory concentrations.
Publication Date: 2001-03-30 PubMed ID: 11277194DOI: 10.2460/ajvr.2001.62.320Google Scholar: Lookup
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  • Journal Article

Summary

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The research is about estimating the chances of surpassing a certain concentration of furosemide in horses after intravenous injection. It’s discovered that these chances decrease over time and increase with dosage.

Study Design and Methodology

  • The investigation involved 12 mature healthy horses, a mix of Thoroughbreds and Quarter Horses.
  • Venous blood was collected from each horse before and at several intervals over a period of 6 hours after the administration of furosemide (either 250 mg or 500 mg).
  • Furosemide concentrations were determined through the enzyme-linked immunosorbent assay (ELISA) technique.
  • The concentration of furosemide was modeled as a function of time, accommodating both inter (among different horses) and intra (within the same horse) variability.

Pharmacokinetic Modeling and Analysis Method

  • A semi-parametric smooth functional averaging method was used for estimating the probability of exceeding a threshold concentration of 100 ng/ml as a function of time based on the pharmacokinetic data.
  • A bootstrap approach, a resampling technique used to estimate statistics on a population by sampling a dataset with replacement, was applied to evaluate the inherent variation in this estimated probability.

Results

  • The calculated probability of surpassing the threshold concentration of 100 ng of furosemide per ml, ranged from 11.6% at 4 hours to 2.2% at 5.5 hours after administering 250mg of furosemide per horse.
  • The same probability was found to be ranging from 34.2% at 4 hours to 12.3% at 5.5 hours after giving an IV of 500 mg of furosemide per horse.
  • The probability of a horse being falsely identified in violation of regulatory concentrations is inversely associated with the time elapsed since administration and directly associated with the dose administered.

Conclusion

  • The study concluded that due to the variability in how different horses process furosemide, some horses may be incorrectly classified as exceeding the regulatory concentrations.

Cite This Article

APA
Cohen ND, Chu KK, Stanley SD, Wang N. (2001). Estimation of the probability for exceeding a threshold concentration of furosemide at various intervals after intravenous administration in horses. Am J Vet Res, 62(3), 320-325. https://doi.org/10.2460/ajvr.2001.62.320

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 62
Issue: 3
Pages: 320-325

Researcher Affiliations

Cohen, N D
  • Department of Large Animal Medicine & Surgery, College of Veterinary Medicine, Texas A&M University, College Station 77843, USA.
Chu, K K
    Stanley, S D
      Wang, N

        MeSH Terms

        • Animals
        • Diuretics / administration & dosage
        • Diuretics / blood
        • Enzyme-Linked Immunosorbent Assay / veterinary
        • False Negative Reactions
        • Female
        • Furosemide / administration & dosage
        • Furosemide / blood
        • Horses / blood
        • Injections, Intravenous / veterinary
        • Models, Statistical
        • Time Factors

        Citations

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