Lauren V. Schnabel¹, Ashlee E.Watts¹, Lisa A. Fortier¹, Mark Papich², Christopher J. Torre¹, Hussni O.Mohammed¹.
¹Cornell University, Ithaca, NY, United States, ²North Carolina State University, Raleigh, NC, United States

ACVS Abstract 2007 

Tetracycline antibiotics have been used to alleviate symptoms and slow the progression of osteoarthritis (OA) and rheumatoid arthritis in human beings. In vitro studies indicate that doxycycline at concentrations of 0.0462 mg/mL significantly decreases matrix metalloproteinase-3 (MMP-3) and MMP-13 gene expression in equine synoviocytes treated with either interleukin-1 or MMP-13. The purpose of this study was to determine if orally administered, low-dose doxycycline could achieve anti-MMP concentrations in synovial fluid and plasma in horses.

Six healthy adult horses without evidence of joint disease or lameness received doxycycline (5mg/kg every 12 hours via nasogastric intubation). Venous blood and synovial fluid samples were collected t=0, and then at t=0.25, 0.5, 1, 12, 24, 48 and 72 hours after doxycycline administration. Doxycycline concentrations were measured using HPLC. Doxycycline concentration in the plasma of all horses was above 0.2146 mg/ mL by t=0.5 hours (mean 0.2550 mg/mL _ 0.0228).

At time points _ t=12 hours, the mean concentration was 0.1018mg/mL _ 0.0193. Synovial fluid concentrations of doxycycline in all horses were above 0.1227mg/mL by t=1 hour (mean 0.1943 _ 0.0279 mg/mL). At each time point after t=1 hour, the mean synovial concentration was 0.2153 mg/mL _ 0.0180. This study suggests that intra-gastric administration of low-dose doxycycline results in synovial fluid doxycycline concentrations sufficient (in vitro) to decrease cartilage catabolism through inhibition of MMPs. However, further in vivo studies are warranted to determine if MMP activity is inhibited in vivo and to elucidate a medication protocol.