title: Pharmacokinetics and effects on thromboxane B2 production following intravenous administration of flunixin meglumine to exercised thoroughbred horses.
abstract: Flunixin meglumine is commonly used in horses for the treatment of musculoskeletal injuries. The current ARCI threshold recommendation is 20 ng/mL when administered at least 24 h prior to race time. In light of samples exceeding the regulatory threshold at 24 h postadministration, the primary goal of the study reported here was to update the pharmacokinetics of flunixin following intravenous administration, utilizing a highly sensitive liquid chromatography-mass spectrometry (LC-MS). An additional objective was to characterize the effects of flunixin on COX-1 and COX-2 inhibition when drug concentrations reached the recommended regulatory threshold. Sixteen exercised adult horses received a single intravenous dose of 1.1 mg/kg. Blood samples were collected up to 72 h postadministration and analyzed using LC-MS. Blood samples were collected from 8 horses for determination of TxB(2) and PGE(2) concentrations prior to and up to 96 h postflunixin administration. Mean systemic clearance, steady-state volume of distribution and terminal elimination half-life was 0.767 ± 0.098 mL/min/kg, 0.137 ± 0.12 L/kg, and 4.8 ± 1.59 h, respectively. Four of the 16 horses had serum concentrations in excess of the current ARCI recommended regulatory threshold at 24 h postadministration. TxB(2) suppression was significant for up to 24 h postadministration.
authors.affiliation: K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.|Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: H K
authors.initials: HK
authors.lastname: Knych
authors.affiliation: School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Arthur
authors.affiliation: K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: McKemie
authors.affiliation: K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Chapman
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D003002:Clonixin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D006736:Horses / Q000097:blood / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D005082:Physical Exertion / Q000502:physiology*; D013929:Thromboxane B2 / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013929:Thromboxane B2; C014558:flunixin meglumine; D003002:Clonixin