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Journal of veterinary internal medicine2018; 32(4); 1428-1435; doi: 10.1111/jvim.15213

Pharmacokinetic and pharmacodynamic properties of orally administered torsemide in healthy horses.

Abstract: Diuretic treatment is the mainstay for management of congestive heart failure in horses, and its use has been restricted to injectable medications because no currently data supports the use of PO administered loop diuretics. Objective: To determine the pharmacokinetic and pharmacodynamic properties of PO administered torsemide and, determine if PO administered torsemide, could be used as an alternative to injectable diuretics in the horse. Methods: Six healthy adult mares. Methods: A 2-phase, prospective study, that consisted of pharmacokinetic profiling of a single dose (6 mg/kg PO) and pharmacodynamic effects of long-term torsemide administration (2 mg/kg PO q12h) for 6 days in healthy horses. Results: Pharmacokinetic analysis identified a peak concentration (C ) of 10.14 µg/mL (range, 6.79-14.69 µg/mL) and elimination half-life (T ) 9.2 hours (range, 8.4-10.4 hours). The area under the plasma drug concentration over time curve (AUC) was 80.7 µg × h/mL (range, 56.5-117.2 µg × h/mL). A statistically significant increase in urine volume and decrease in urine specific gravity were found from day 0 (baseline) to day 6 (P < .0001). Significant alterations in biochemical variables included hyponatremia, hypokalemia, hypochloremia, and increased serum creatinine concentration. Mean arterial blood pressure significantly decreased on day 6 (57.7 ± 8.8 mm Hg, P = .001) as compared with baseline (78 ± 6.1 mm Hg). Serum aldosterone concentrations significantly increased after 6 days of torsemide administration (P = .0006). Conclusions: PO administered torsemide (4 mg/kg/day) successfully reached therapeutic concentrations in blood, induced clinically relevant diuresis, and resulted in moderate pre-renal azotemia and electrolyte disturbances.
Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
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Publication Date: 2018-05-17 PubMed ID: 29770976PubMed Central: PMC6060311DOI: 10.1111/jvim.15213Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the effects of orally-administered torsemide, a diuretic medication, in horses. It specifically explores its efficiencies and changes it induces in the cardiovascular system of the animals, with the intention of establishing whether it can serve as a potential alternative for injectable diuretics, commonly used in managing congestive heart failure in these animals.

Objectives and Methodology

The research aims to evaluate two key aspects:

  • The dynamics of absorption, concentration, and removal of torsemide in the horse’s system—otherwise known as pharmacokinetic properties.
  • The impact and response of the horse’s body to torsemide—pharmacodynamic properties.

The study was carried out in two phases with six healthy adult female horses. The first phase involved administering a single dosage of torsemide and observing its pharmacokinetic profiling. The second involved long-term administration of torsemide and evaluating its effects on the horses.

Results

Several outcomes were observed from the single dosage and the long-term administration of torsemide:

  • The drug reached a peak level in the blood and was gradually eliminated from the body with an estimated half-life of about 9.2 hours.
  • A substantial increase in urine volume and a decrease in urine specific gravity were noted, implying effective diuretic action.
  • Significant changes in blood biochemistry were spotted, including reductions in sodium (hyponatremia), potassium (hypokalemia), chloride (hypochloremia) levels, and an increased concentration of creatinine, a waste product usually filtered out by the kidneys.
  • A noticeable decrease in mean arterial blood pressure was reported on the sixth day as compared to the baseline.
  • An increase in serum aldosterone, a hormone that helps regulate sodium salts and water balance in the body, was recorded after six days of torsemide administration.

Conclusions

The researchers concluded that orally administered torsemide effectively reached therapeutic concentrations in the blood, triggering clinically relevant diuresis (increased urine production). It also induced moderate pre-renal azotemia (increased levels of nitrogen waste in the blood) and caused disruptions in electrolyte balance. The research concluded torsemide could be a potential alternative to injectable diuretics for the management of congestive heart failure in horses, as it demonstrated effectiveness in inducing diuresis. However, close attention would be needed to monitor and manage the side effects such as electrolyte imbalance and changes in kidney function.

Cite This Article

APA
Agne GF, Jung SW, Wooldridge AA, Duran SH, Ravis W, Toribio R. (2018). Pharmacokinetic and pharmacodynamic properties of orally administered torsemide in healthy horses. J Vet Intern Med, 32(4), 1428-1435. https://doi.org/10.1111/jvim.15213

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 32
Issue: 4
Pages: 1428-1435

Researcher Affiliations

Agne, Gustavo F
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, Alabama.
Jung, Seung Woo
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, Alabama.
Wooldridge, Anne A
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, Alabama.
Duran, Susan H
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, Alabama.
Ravis, William
  • Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama.
Toribio, Ramiro
  • Department of Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio.

MeSH Terms

  • Administration, Oral
  • Animals
  • Chlorides / blood
  • Creatinine / blood
  • Diuretics / administration & dosage
  • Diuretics / blood
  • Diuretics / pharmacokinetics
  • Diuretics / pharmacology
  • Female
  • Half-Life
  • Horse Diseases / chemically induced
  • Horses / blood
  • Horses / metabolism
  • Hypokalemia / chemically induced
  • Hypokalemia / veterinary
  • Hyponatremia / chemically induced
  • Hyponatremia / veterinary
  • Sulfonamides / administration & dosage
  • Sulfonamides / blood
  • Sulfonamides / pharmacokinetics
  • Sulfonamides / pharmacology
  • Torsemide

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Citations

This article has been cited 1 times.
  1. Scantamburlo G, Nofziger C, Paulmichl M, Vanoni S. Genetic analysis of the equine orthologues for human CYP2D6: unraveling the complexity of the CYP2D family in horses. Front Vet Sci 2023;10:1188633.
    doi: 10.3389/fvets.2023.1188633pubmed: 37929279google scholar: lookup
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