Disposition of methylprednisolone acetate in plasma, urine, and synovial fluid following intra‐articular administration to exercised thoroughbred horses

Abstract

Methylprednisolone acetate (MPA) is commonly administered to performance horses, and therefore, establishing appropriate withdrawal times prior to performance is critical. The objectives of this study were to describe the plasma pharmacokinetics of MPA and time-related urine and synovial fluid concentrations following intra-articular administration to sixteen racing fit adult Thoroughbred horses. Horses received a single intra-articular administration of MPA (100 mg). Blood, urine, and synovial fluid samples were collected prior to and at various times up to 77 days postdrug administration and analyzed using tandem liquid chromatography-mass spectrometry (LC-MS/MS). Maximum measured plasma MPA concentrations were 6.06 ± 1.57 at 0.271 days (6.5 h; range: 5.0-7.92 h) and 6.27 ± 1.29 ng/mL at 0.276 days (6.6 h; range: 4.03-12.0 h) for horses that had synovial fluid collected (group 1) and those that did not (group 2), respectively. The plasma terminal half-life was 1.33 ± 0.80 and 0.843 ± 0.414 days for groups 1 and 2, respectively. MPA was undetectable by day 6.25 ± 2.12 (group 1) and 4.81 ± 2.56 (group 2) in plasma and day 17 (group 1) and 14 (group 2) in urine. MPA concentrations in synovial fluid remained above the limit of detection (LOD) for up to 77 days following intra-articular administration, suggesting that plasma and urine concentrations are not a good indicator of synovial fluid concentrations.

Pharmacokinetics of betamethasone in plasma, urine, and synovial fluid following intra‐articular administration to exercised thoroughbred horses

“…Similar to what has been reported for other intra-articular corticosteroids in horses, [7,8,12] plasma betamethasone concentrations are not reflective of concentrations in the joint and therefore are likely not a good indicator of the duration of effect of intra-articular corticosteroids. In the current study, concentrations of betamethasone in plasma fell below detectable levels at 72 h post administration in 10/12 horses, at which time concentrations in the treated joint (right radiocarpal joint) were still well above the LOD of the assay (9.83 ± 10.1 ng/mL).…”

“…Similar findings have been reported for methylprednisolone acetate following intraarticular administration. [8] As was postulated for methylprednisolone acetate, detection of betamethasone concentrations in the right middle carpal is likely attributable to direct transfer from the right antebrachiocarpal joint, however, detection of drug in the joints in the contralateral leg is most likely a result of transfer via the systemic circulation.…”

“…Similarly, methylprednisolone was detected in synovial fluid for up to 77 days post administration of a single dose of methylprednisolone acetate (MPA) while only detected in blood for 14 days. [8] These results suggest that the effects of intra-articular corticosteroids may still be present after drug concentrations have fallen below the limit of detection in blood and that perhaps less frequent or lower dose administration is warranted.…”

“…Blood samples for drug concentration determination were collected at time 0 (prior to drug administration) and at 15, 30, and 45 min, and 1, 1.5, 2, 2.5, 3,4,6,8,12,18,24,36,48,72,96, and 120 h post administration. Subsequent samples were collected on day 7, 8, 9, and 10 post drug administration.…”

“…Both triamcinolone acetonide and methylprednisolone acetate are detected in the joint for prolonged periods of time relative to their detection time in blood or urine. [7,8] Knych et al [7] reported detection of triamcinolone for up to 35 days in synovial fluid while concentrations in the blood were only measurable for 7 days in blood following a single intra-articular administration. Similarly, methylprednisolone was detected in synovial fluid for up to 77 days post administration of a single dose of methylprednisolone acetate (MPA) while only detected in blood for 14 days.…”