Disposition of isoflupredone acetate in plasma, urine and synovial fluid following intra-articular administration to exercised Thoroughbred horses.
The use of isoflupredone acetate in performance horses and the scarcity of published pharmacokinetic data necessitate further study. The objective of the current study was to describe the plasma pharmacokinetics of isoflupredone acetate as well as time-related urine and synovial fluid concentrations following intra-articular administration to horses. Twelve racing-fit adult Thoroughbred horses received a single intra-articular administration (8 mg) of isoflupredone acetate into the right antebrachiocarpal joint. Blood, urine and synovial fluid samples were collected prior to and at various times up to 28 days post drug administration. All samples were analyzed using liquid chromatography-Mass Spectrometry. Plasma data were analyzed using a population pharmacokinetic compartmental model. Maximum measured plasma isoflupredone concentrations were 1.76 ± 0.526 ng/mL at 4.0 ± 1.31 h and 1.63 ± 0.243 ng/mL at 4.75 ± 0.5 h, respectively, for horses that had synovial fluid collected and for those that did not. The plasma beta half-life was 24.2 h. Isoflupredone concentrations were below the limit of detection in all horses by 48 h and 7 days in plasma and urine, respectively. Isoflupredone was detected in the right antebrachiocarpal and middle carpal joints for 8.38 ± 5.21 and 2.38 ± 0.52 days, respectively. Results of this study provide information that can be used to regulate the use of intra-articular isoflupredone in the horse.
K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, 95616, CA, USA.|Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 95616, CA, USA.
Heather K
HK
Knych
Willow Oak Equine, Woodland, 95695, CA, USA.
Linda M
LM
Harrison
K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, 95616, CA, USA.
Alexandria
A
White
K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, 95616, CA, USA.
Daniel S
DS
McKemie
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D005260:Female; D005477:Fluprednisolone / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D005938:Glucocorticoids / Q000032:analysis / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D006736:Horses / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D008297:Male; D015813:Substance Abuse Detection / Q000379:methods; D013582:Synovial Fluid / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods
D005938:Glucocorticoids; C065592:isoflupredone acetate; D005477:Fluprednisolone
corticosteroid; horse, intra-articular; isoflupredone; racehorse