Pharmacokinetics of furosemide in thoroughbred horses subjected to supramaximal treadmill exercise with and without controlled access to water.
Abstract: The primary objective of this study was to assess the disposition of furosemide in Thoroughbred horses treated intravenously with 1 mg/kg of furosemide 4 and 24 h before supramaximal treadmill exercise without and with controlled access to water, respectively. Another objective was to determine whether furosemide was detectable in the plasma of horses after exposure to supramaximal treadmill exercise. Thoroughbred horses (n = 4-6) were administered single intravenous doses of 1 mg/kg of furosemide at 4 and 24 h before supramaximal exercise on a high-speed treadmill, with controlled and free access to water, respectively. Plasma furosemide concentrations were determined using liquid chromatography. Results: Furosemide was detected in all the horses, regardless of whether they were treated 24 h or 4 h before excersice. In both treatment sequence groups of 2 horses, the concentration time profiles of furosemide during the first 4 h after its administration were relatively similar. The average maximum observed concentrations, AUC and AUC, of both groups of horses were not different (p > 0.05). There were no significant differences in systemic clearance based on the geometric mean (95% confidence interval) (409 (347-482) mL/h/kg) for 4 h and 320 (177-580) mL/h/kg) for 24 h) between horses that were exercised 4- and 24-h post-furosemide administration. The plasma concentration of furosemide in all the horses fell below the limit of quantification (25 ng/mL) within 12 h after drug administration. In the group treated 24 h before exercise, none of the horses had detectable furosemide at the time of supramaximal treadmill exercise. In the group treated 4 h before exercise, furosemide was detected 1 h before and 2 h after supramaximal treadmill exercise in 4/4 and 3/4 horses, respectively. The mean AUC of both groups of horses were not different (p > 0.05). Conclusions: Water restriction did not exert any apparent effect on the disposition of furosemide. It remains to be determined, however, whether the attained plasma concentration of furosemide in combination with other controlled water access protocols have any direct or indirect pharmacological effect that may affect the athletic performance of the horse.
Publication Date: 2019-08-02 PubMed ID: 31375096PubMed Central: PMC6679487DOI: 10.1186/s12917-019-2017-3Google Scholar: Lookup
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- Clinical Trial
- Veterinary
- Journal Article
Summary
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The research examined how the drug furosemide behaves in Thoroughbred horses put through intense treadmill exercise, with a particular focus on whether their water intake had any effect. Furosemide was found in the plasma of the horses regardless of when they had been administered the drug and it seems that limiting water intake did not alter the disposition of furosemide although its effects on athletic performance require further study.
Objective and Method
- The study had two main objectives. Firstly, it aimed to investigate the behavior or disposition of the drug furosemide when administered 4 and 24 hours before an intense round of exercise in Thoroughbred horses. Secondly, it hoped to establish whether furosemide remained in the horses’ plasma after this exercise.
- Horses were given a single intravenous dose of the drug and then undertook intense treadmill exercise. The exercise protocol was standardised, and was considered ‘supramaximal’ – more intense than the horse would naturally choose to perform.
- The horses were assigned different water intake conditions. Some had free access to water, whilst others had their access controlled.
Results
- Furosemide was detected in all horses, regardless of their pre-exercise administration time and water intake conditions. The concentration levels of the drug over the initial 4 hours after administration did not significantly vary.
- There were no significant differences in the rates of systemic clearance for the drug, meaning how quickly it was processed and removed from the horse’s body. The plasma concentration of furosemide fell below 25ng/mL within 12 hours after administration in all horses.
- In the group of horses given the drug 24 hours before exercise, none had detectable furosemide at the time of exercise. However, in the group given the drug 4 hours before exercise, the drug was found in their systems 1 hour before and 2 hours after exercise.
Conclusion
- Overall, the study found that restricting water intake did not seem to have any noticeable effect on the behavior of the drug furosemide in the horses’ bodies. This suggests that concerns about the drug’s behavior in dehydrated horses, or those with controlled water intake, may be unnecessary.
- However, this doesn’t resolve the question of whether the drug’s presence, combined with potential thirst, affects the horses’ athletic performance. Further investigations would be needed to assess these potential impacts.
Cite This Article
APA
Villarino NF, Lopez CM, Sams RA, Bayly WM.
(2019).
Pharmacokinetics of furosemide in thoroughbred horses subjected to supramaximal treadmill exercise with and without controlled access to water.
BMC Vet Res, 15(1), 275.
https://doi.org/10.1186/s12917-019-2017-3 Publication
Researcher Affiliations
- Program in Individualized Medicine, Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA, 99164-6610, USA.
- Department of Veterinary Clinical Sciences, Washington State University, PO Box 646610, Pullman, WA, 99164-6610, USA.
- LGC Science Inc., Lexington, KY, 40509, USA.
- Department of Veterinary Clinical Sciences, Washington State University, PO Box 646610, Pullman, WA, 99164-6610, USA. wmb@vetmed.wsu.edu.
MeSH Terms
- Animals
- Area Under Curve
- Diuretics / blood
- Diuretics / pharmacokinetics
- Female
- Furosemide / blood
- Furosemide / pharmacokinetics
- Horses / blood
- Male
- Physical Conditioning, Animal
- Water-Electrolyte Balance
Grant Funding
- ' / Grayson-Jockey Club Research Foundation
- ' / American Association of Equine Practitioners Foundation
- ' / Churchill Downs
- ' / Del Mar Thoroughbred Club
- ' / Keeneland Racetrack
- ' / Kentucky Downs
- ' / The Stronach Group
- ' / New York Racing Association
- ' / Oak Tree Racing Association
- ' / Oaklawn Racetrack
- ' / the Thoroughbred Horseman's Association
- ' / the Washington State University College of Veterinary Medicine Equine Research Program.
Conflict of Interest Statement
Dr. Bayly is a former member of the Board of Directors of the American Association of Equine Practitioners. Dr. Bayly is currently a member of the Grayson-Jockey Club Research Advisory Committee, but was not at the time of funding. The other authors have no conflicts of interest.
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This article includes 19 references
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Citations
This article has been cited 1 times.- Banihashemi SH, Samimi AS, Samimi K, Tajik J. Effects of double intravenous furosemide administration at different doses on clinical variables, electrocardiographic indices and serum electrolytes in miniature donkeys.. Vet Res Forum 2023;14(1):53-57.
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