Synovial distribution of “systemically” administered acetylsalicylic acid in the isolated perfused equine distal limb

BACKGROUND: This study investigated synovial concentrations of acetylsalicylic acid (ASA) and its metabolite salicylic acid (SA) in the equine fetlock joint following systemic administration of ASA. Salicylates were chosen because SA is the only nonsteroidal anti-inflammatory drug for which threshold levels exist for plasma and urine in equine sports. To avoid animal experiments, the study was conducted using an ex vivo model of the isolated perfused equine distal limb in combination with plasma concentrations obtained from literature. Salicylate concentrations in the joint were determined using microdialysis and high performance liquid chromatography (HPLC). Any anti-inflammatory effect of synovial ASA concentrations was assessed using an ASA EC(50) (half maximal effective concentration) determined in equine whole blood. RESULTS: The ASA concentration in the synovial fluid (n = 6) reached a maximum of 4 μg/mL, the mean concentration over the entire perfusion period was 2 μg/mL. Maximum SA concentration was 17 μg/mL, the average was 14 μg/mL. ASA and SA concentration in the synovial fluid exceeded systemic concentrations 2 h and 3.5 h after “systemic” administration, respectively. CONCLUSIONS: ASA and SA accumulated in the in the synovial fluid of the ex vivo model despite decreasing systemic concentrations. This suggests a prolonged anti-inflammatory effect within the joint that remains to be further elucidated.