title: 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.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Johansson
authors.forename: Sarah Y
authors.initials: SY
authors.lastname: Gardner
authors.forename: Jay F
authors.initials: JF
authors.lastname: Levine
authors.forename: Mark G
authors.initials: MG
authors.lastname: Papich
authors.forename: D Heath
authors.initials: DH
authors.lastname: Lafevers
authors.forename: Rebecca B
authors.initials: RB
authors.lastname: Goldman
authors.forename: M Katie
authors.initials: MK
authors.lastname: Sheets
authors.forename: Clarke E
authors.initials: CE
authors.lastname: Atkins
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004232:Diuretics / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D005665:Furosemide / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous / Q000662:veterinary; D013046:Specific Gravity / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D004232:Diuretics; D005665:Furosemide