Pharmacokinetics and effects on thromboxane B2 production following intravenous administration of flunixin meglumine to exercised thoroughbred horses

Flunixin meglumine is commonly used in horses for the treatment of musculoskeletal injuries. The current ARCI threshold recommendation is 20ng/mL when administered at least 24h prior to race time. In light of samples exceeding the regulatory threshold at 24h 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 1.1mg/kg. Blood samples were collected up to 72h 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 96h postflunixin administration. Mean systemic clearance, steady-state volume of distribution and terminal elimination half-life was 0.767 +/- 0.098mL/min/kg, 0.137 +/- 0.12L/kg, and 4.8 +/- 1.59h, respectively. Four of the 16 horses had serum concentrations in excess of the current ARCI recommended regulatory threshold at 24h postadministration. TxB(2) suppression was significant for up to 24h postadministration.