In Vivo Joint Synovial Fluid Disposition of a Novel Sustained-Release Formulation of Diclofenac and Hyaluronic Acid in Horses.

Intra-articular administration of sustained-release anti-inflammatory drugs is indicated in horses suffering from joint inflammation, but no such drugs are labelled for veterinary use. To obtain initial data on synovial disposition and safety of a new sustained-release formulation of diclofenac (SYN321) in the joints of horses, an experimental interventional study of elimination and side effects of intra-articular administration of SYN321 was conducted. Nine clinically sound horses were included in the study, and SYN321 was administered by the intra-articular route. Dose ranges and sampling intervals were established in a pilot study with two horses, and then applied in a main study involving seven horses treated in the fetlock joint. Diclofenac was detected above lower limit of quantification (LOQ: 0.5 ng/ml) in synovial fluid throughout the study period (14 days), and below LOQ (0.1 ng/ml) in plasma after 4 days and in urine after 14 days. No obvious clinical side effects were detected. Clinical examination and objective lameness evaluation suggested that SYN321 has potential as a local joint NSAID treatment with sustained release in horses, but further studies on synovial fluid exposure, safety and clinical efficacy are warranted.