title: Detection, quantification, and pharmacokinetics of furosemide and its effects on urinary specific gravity following IV administration to horses.
abstract: Furosemide is a potent loop diuretic used for the prevention of exercise-induced pulmonary hemorrhage in horses. This drug may interfere with the detection of other substances by reducing urinary concentrations, so its use is strictly regulated. The regulation of furosemide in many racing jurisdictions is based on paired limits of urinary SG (<1.010) and serum furosemide concentrations (>100 ng/ml). To validate this regulatory mechanism, a liquid chromatography/mass spectrometry/mass spectrometry method employing a solid-phase extraction procedure and furosemide-d5 as an internal standard was developed. The method was used to determine the pharmacokinetic parameters of furosemide in equine serum samples and its effects on urinary SG after IV administration (250 mg) to 10 horses. Pharmacokinetic analysis showed that serum concentrations of furosemide were well described by a two-compartmental open model. Based on results in this study, it is very unlikely for horses to have serum furosemide concentrations greater than 100 ng/ml or urine SG less than 1.010 at 4 hours after administration (250 mg IV). However, it should be remembered that urine SG is a highly variable measurement in horses, and even without furosemide administration, some horses might naturally have urine SG values less than 1.010.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Nursing and Allied Health, Tuskegee University, Tuskegee, AL 36088, USA.
authors.forename: Levent
authors.initials: L
authors.lastname: Dirikolu
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Lehner
authors.forename: Charlie
authors.initials: C
authors.lastname: Hughes
authors.forename: Wojciech
authors.initials: W
authors.lastname: Karpiesiuk
authors.forename: Fernanda C
authors.initials: FC
authors.lastname: Camargo
authors.forename: J Daniel
authors.initials: JD
authors.lastname: Harkins
authors.forename: William E
authors.initials: WE
authors.lastname: Woods
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Bosken
authors.forename: Jeff
authors.initials: J
authors.lastname: Boyles
authors.forename: Amy
authors.initials: A
authors.lastname: Troppmann
authors.forename: Mitzi
authors.initials: M
authors.lastname: Fisher
authors.forename: Thomas
authors.initials: T
authors.lastname: Tobin
mesh_terms: D000818:Animals; D019540:Area Under Curve; D004232:Diuretics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006736:Horses / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007262:Infusions, Intravenous / Q000662:veterinary; D013046:Specific Gravity / Q000187:drug effects
chemical_list: D004232:Diuretics; D005665:Furosemide