Pharmacokinetics of triamcinolone acetonide following intramuscular and intra-articular administration to exercised Thoroughbred horses H. K. KNYCH* †‡ , M. A. VIDAL § , H. C. CASBEER † and D. S. McKEMIE † † K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, USA ‡ Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, USA § Department of Surgery and Radiology, School of Veterinary Medicine, University of California, USA. *Correspondence email: hkknych@ucdavis.edu; Received: 27.11.12; Accepted: 27.01.13 Summary Reason for performing study: The use of triamcinolone acetonide (TA) in performance horses necessitates establishing appropriate withdrawal times prior to performance. Objectives: To describe the plasma pharmacokinetics of TA and time-related urine and synovial fluid concentrations following i.m. and intra-articular administration to exercised Thoroughbred horses. Study design: Block design. Methods: Twelve racing fit adult Thoroughbred horses received a single i.m. administration of TA (0.1 mg/kg bwt). After an appropriate washout period, the same horses then received a single intra-articular TA administration (9 mg) into the right antebrachiocarpal joint. Blood, urine and synovial fluid samples were collected prior to, and at various times, up to 60 days post drug administration and analysed using liquid chromatography-mass spectrometry. Plasma data were analysed using noncompartmental analysis. Results: Maximum measured plasma TA concentrations were 0.996  0.391 at 13.2 h and 1.27  0.278 ng/ml at 6.5 h for i.m. and intra-articular administration, respectively. The plasma terminal elimination half-life was 11.4  6.53 and 0.78  1.00 days for i.m. and intra-articular administration, respectively. Following i.m. administration, TA was below the limit of detection (LOD) by Days 52 and 60 in plasma and urine, respectively. Following intra-articular administration TA was undetectable by Day 7 in plasma and Day 8 in urine. Triamcinolone acetonide was also undetectable in any of the joints sampled following i.m. administration and remained above the limit of quantitation (LOQ) for 21 days following intra-articular administration. Conclusions and potential relevance: This study extends previous studies describing the pharmacokinetics of TA following i.m. and intra-articular administration to the horse and suggests that plasma and urine concentrations are not a good indicator of synovial fluid concentrations. Furthermore, results of this study supports an extended withdrawal time for TA given i.m. The Summary is available in Chinese – see Supporting information. Keywords: horse; pharmacokinetics; Thoroughbred; triamacinolone acetonide (TA); corticosteroid; syonvial fluid Introduction It is of paramount importance to regulate the use of drugs that have the potential to mask performance-limiting injuries. However, determining threshold values and withdrawal guidelines for drugs administered prior to performance proves to be a constant challenge for regulatory agencies. This is especially true with the advent of increasingly sensitive analytical instrumentation that can detect picogram levels of drugs in biological samples. The increased sensitivity of analytical instrumentation necessitates periodic reassessment of the pharmacokinetics and relevant drug withdrawal times to minimise inadvertent positive findings. Corticosteroids, such as triamcinolone, are potent anti-inflammatory agentsusedinhorsestotreatperformance-relatedinjuries.Triamcinoloneis classified as a Class 4 (Penalty Class C) foreign substance by the Association of Racing Commissioners International and its use close to competition is of particular concern to regulatory agencies. Triamcinolone has been found to be an effective analgesic and anti-inflammatory agent in both an osteochondral fragmentation model [1] and an acute lipopolysaccharide- induced lameness model [2]. Intra-articular triamcinolone acetonide (TA) reduces lameness and favourably affects synovial fluid, synovial membrane and morphological parameters of articular cartilage compared with the placebo treatment [1]. Triamcinolone acetonide reportedly also has a favourable ‘remote administration’ effect in the joint contralateral to the treated joint following intra-articular administration [1]. The pharmacokinetics of TA following i.m. and intra-articular administration in the horse has been previously reported [3,4]. Following i.m. administration of TA (0.2 mg/kg bwt), French and colleagues [3] reported plasma concentrations that were below the limit of detection (LOD) (1 ng/ml) by 5 h post administration. In a second study describing the pharmacokinetics of i.m. TA (0.04 mg/kg bwt) in horses, Soma and colleagues [4] reported a maximum plasma concentration of 0.34 ng/ml with detection of TA for 15 days post administration. The reported elimination half-life was 150.2 h. The same authors reported a plasma elimination half-life of 23.8 h after intra-articular administration of TA (0.04 mg/kg bwt) into the carpal joint [4]. Maximal plasma concentrations were 2.0 ng/ml at 10 h post administration [3]. Chen et al. [5] reported maximal concentrations of 4.3 ng/ml at 4 h post administration following an intra-articular dose of TA (6 mg) administered at 3 different sites with plasma concentrations at almost nondetectable levels by 2 days post administration [5]. There are limited reports describing synovial fluid concentrations of TA following intra-articular administration [2,5]. Kay and colleagues detected TA in synovial fluid for up to 240 h post administration (the last time point collected) following intra-articular administration (9 mg) into a single joint [2]. Chen et al. [5] reported detectable TA concentrations in synovial fluid for 15 days following intra-articular administration. Previous studies have assessed TA concentrations in blood [3,4]. However, in many racing jurisdictions, urine is the matrix of choice for testing for illegal substances, necessitating study of urinary concentrations. Therefore the primary objective in the present study was to determine plasma and urine concentrations of TA following i.m. and intra-articular administration to exercised horses. Additionally, for both routes of administration, synovial fluid concentrations of TA over time were measured. Materials and methods Horses and drug administration Twelve healthy exercised to racing fitness adult Thoroughbred horses including 6 geldings and 6 mares (3–6 years) were studied. Prior to, Equine Veterinary Journal ISSN 0425-1644 DOI: 10.1111/evj.12059 715 Equine Veterinary Journal 45 (2013) 715–720 © 2013 EVJ Ltd