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In vivo kinetic study on uptake and distribution of intramuscular tritium-labeled polysulfated glycosaminoglycan in equine body fluid compartments and articular cartilage in an osteochondrial defect model
Authors:Daniel J Burba DVM  Michael A Collier DVM  Lawrence E Default PhD  Olivia Hanson-Painton PhD  Harold C Thompson Jr and Claude L Holder
Institution:

1Department of Equine Surgery and Medicine, Boren Veterinary Medical Teaching Hospital, College of Veterinary Medicine, Oklahoma State University, Stillwater, Oklahoma.

3Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas.

4Department of Pathology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK.

&Present Address: School of Veterinary Medicine, Department of Veterinary Clinical Sciences, Louisiana State University, Baton Rouge, LA.

Abstract:The uptake and distribution of intramuscularly (IM) administered tritium-labeled polysulfated glycosaminoglycan (3H-PSGAG) in serum, synovial fluid, and articular cartilage of eight horses was quantitated, and hyaluronic acid (HA) concentration of the middle carpal joint was evaluated in a pharmacokinetic study. A full-thickness articular cartilage defect, created on the distal articular surface of the left radial carpal bone of each horse served as an osteochondral defect model. 3H-PSGAG (500 mg) was injected IM, between 14 and 35 days after creation of the defects. Scintillation analysis of serum and synovial fluid, collected from both middle carpal joints at specific predetermined times up to 96 hours post-injection, revealed mean 3H-PSGAG concentrations peaked at 2 hours post-injection. 3H-PSGAG was detected in cartilage and subchondral bone 96 hours post-injection in samples from all eight horses. There were no statistically significant differences in 3H-PSGAG concentration of synovial fluid or cartilage between cartilage defect and control (right middle carpal) joints.

HA assay of synovial fluid revealed concentrations significantly increased at 24, 48, and 96 hours post-injection in both joints. The concentration nearly doubled 48 hours post-injection. However, no statistically significant differences were found between synovial concentrations of HA in cartilage defect and control joints.

3H-PSGAG administered IM to horses, was distributed in the blood, synovial fluid, and articular cartilage. HA concentrations in synovial fluid increased after IM administration of polysulfated glycosaminoglycan.

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