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.

Pharmacokinetic and pharmacodynamic properties of orally administered torsemide in healthy horses

“…Frequent IM or IV administration of furosemide can lead to complications such as local infection, perivascular administration of the drug, thrombosis and accidental injection into the carotid artery . A pharmacokinetic and pharmacodynamic study of PO furosemide in healthy horses indicated that the bioavailability of PO furosemide using a single dose of 1 mg/kg was only 5% . In the same study, no differences in urine volume and plasma electrolyte concentrations were noted after PO furosemide administration when compared with control horses.…”

“…14 A pharmacokinetic and pharmacodynamic study of PO furosemide in healthy horses indicated that the bioavailability of PO furosemide using a single dose of 1 mg/kg was only 5%. 1 In the same study, no differences in urine volume and plasma electrolyte concentrations were noted after PO furosemide administration when compared with control horses.…”

“…With the current availability of effective formulations of other cardiovascular medications, such as ACE inhibitors, for PO use, and the tendency to keep horses long term as companion animals, horse owners maybe more amenable to treat chronic medical conditions such as CHF . A diuretic drug such as torsemide, which potentially can provide better quality of life, less risk of cardiac remodeling, less diuretic resistance, and better owner compliance without the need for an injectable treatment regimen, can be an important addition in the treatment of CHF in the horse …”

“…Fluid overload occurs with various conditions in the horse including congestive heart failure (CHF), pulmonary edema, distal limb cellulitis, head trauma, and respiratory distress syndrome in foals . Loop diuretics (eg, furosemide, torsemide) have been used for clinical conditions in horses, humans, dogs, and cats to remove excessive fluid from the body by blocking the Na‐K‐2Cl transporters in the thick ascending loop of Henle.…”

Pharmacokinetics of single doses of maropitant citrate in adult horses

“…(13.31 ± 5.30%), compared to dogs (23.7% [19.9%-28.3%]) and cats (50%) (Benchaoui et al, 2007;Hickman et al, 2008). This finding of reduced bioavailability of orally administered drugs in horses is common and has been found with numerous pharmaceuticals, including furosemide, tramadol, cephalexin, and minocycline (Davis, Salmon, & Papich, 2005;Echeverria, Lascola, Giguere, & Foreman, 2018;Johannson et al, 2004;Shilo et al, 2008). The reasons for this species difference are unknown.…”