Pharmacokinetics and pharmacodynamics of furosemide after oral administration to horses.
Abstract: Furosemide is the most common diuretic drug used in horses. Furosemide is routinely administered as IV or IM bolus doses 3-4 times a day. Administration PO is often suggested as an alternative, even though documentation of absorption and efficacy in horses is lacking. This study was carried out in a randomized, crossover design and compared 8-hour urine volume among control horses that received placebo, horses that received furosemide at 1 mg/kg PO, and horses that received furosemide at 1 mg/kg IV. Blood samples for analysis of plasma furosemide concentrations, PCV, and total solids were obtained at specific time points from treated horses. Furosemide concentrations were determined by reversed-phase high-performance liquid chromatography with fluorescent detection. Systemic availability of furosemide PO was poor, erratic, and variable among horses. Median systemic bioavailability was 5.4% (25th percentile, 75th percentile: 3.5, 9.6). Horses that received furosemide IV produced 7.4 L (7.1, 7.7) of urine over the 8-hour period. The maximum plasma concentration of 0.03 microg/mL after administration PO was not sufficient to increase urine volume compared with control horses (1.2 L [1.0, 1.4] PO versus 1.2 L [1.0, 1.4] control). There was a mild decrease in urine specific gravity within 1-2 hours after administration of furosemide PO, and urine specific gravity was significantly lower in horses treated with furosemide PO compared with control horses at the 2-hour time point. Systemic availability of furosemide PO was poor and variable. Furosemide at 1 mg/kg PO did not induce diuresis in horses.
Publication Date: 2004-11-02 PubMed ID: 15515593DOI: 10.1892/0891-6640(2004)18<739:papofa>2.0.co;2Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study investigates the pharmacokinetics (the movement of drug within the body) and pharmacodynamics (the physiological effects of the drug) of oral administration of furosemide, a common diuretic drug for horses. The results indicate that oral administration of the drug has poor and variable availability in the system, leading to ineffective diuresis (increased production of urine) compared to intravenous administration.
Methodology and Results: Comparing Oral and Intravenous Furosemide Administration
- The experimental setup involved a randomized, crossover design to compare the effects of both oral and intravenous administration of furosemide.
- The research aimed to measure 8-hour urine volume in three groups of horses: those receiving a placebo, those given 1 mg/kg of furosemide orally, and those given the same dose intravenously.
- To determine furosemide concentration, blood samples were drawn at specific time points and analyzed using reversed-phase high-performance liquid chromatography, a method for identifying chemical compounds in a mixture.
- The results showed that the systemic (affecting the whole body) availability of furosemide administered orally was both unreliable and inconsistent across different horses, with a median systemic bioavailability (the proportion of the drug that enters circulation) of just 5.4%.
Insufficient Diuresis Effect of Oral Furosemide Administration
- Horses that were administered the drug intravenously were found to produce significantly more urine over an eight-hour period than horses administered the drug orally.
- The maximum plasma concentration (how much of the drug is in the bloodstream) of 0.03 micrograms/mL achieved through oral administration did not lead to an increase in urine production compared to the control sample (horses without any administered drug).
- A mild decrease in urine specific gravity—a measure of urine concentration—occurred within 1-2 hours following oral administration, although the specific gravity was lower in horses given oral furosemide compared to the control at the 2-hour mark.
Ineffective Results and Conclusion
- Despite these observations, the systemic availability remained poor and inconsistent.
- The study concluded that administering furosemide orally at a dose of 1 mg/kg does not induce diuresis in horses, highlighting the inefficiency of oral administration.
Cite This Article
APA
Johansson AM, Gardner SY, Levine JF, Papich MG, Lafevers DH, Goldman RB, Sheets MK, Atkins CE.
(2004).
Pharmacokinetics and pharmacodynamics of furosemide after oral administration to horses.
J Vet Intern Med, 18(5), 739-743.
https://doi.org/10.1892/0891-6640(2004)18<739:papofa>2.0.co;2 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
MeSH Terms
- Administration, Oral
- Animals
- Biological Availability
- Chromatography, High Pressure Liquid / veterinary
- Diuretics / pharmacokinetics
- Diuretics / pharmacology
- Female
- Furosemide / pharmacokinetics
- Furosemide / pharmacology
- Horses / metabolism
- Injections, Intravenous / veterinary
- Specific Gravity / drug effects
- Treatment Outcome
Citations
This article has been cited 3 times.- Adin D, Kurtz K, Atkins C, Papich MG, Vaden S. Role of electrolyte concentrations and renin-angiotensin-aldosterone activation in the staging of canine heart disease. J Vet Intern Med 2020 Jan;34(1):53-64.
- Villarino NF, Lopez CM, Sams RA, Bayly WM. Pharmacokinetics of furosemide in thoroughbred horses subjected to supramaximal treadmill exercise with and without controlled access to water. BMC Vet Res 2019 Aug 2;15(1):275.
- Agne GF, Jung SW, Wooldridge AA, Duran SH, Ravis W, Toribio R. Pharmacokinetic and pharmacodynamic properties of orally administered torsemide in healthy horses. J Vet Intern Med 2018 Jul;32(4):1428-1435.
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