Orally administered doxycycline accumulates in synovial fluid compared to plasma

Equine Vet J. 2010 Apr;42(3):208-12. doi: 10.2746/042516409X478514.


Reasons for performing study: Tetracycline compounds have been used to slow the progression of osteoarthritis (OA) and rheumatoid arthritis but the concentration of doxycycline attained in synovial fluid following oral, low-dose administration has yet to be determined.

Objective: To determine the concentration of doxycycline in synovial fluid following oral, low-dose administration.

Methods: Six mature horses received doxycycline (5 mg/kg bwt q. 12 h for 5 doses). Venous blood and synovial fluid samples were collected at t=0, 0.25, 0.5, 1, 12, 24, 48 and 72 h. Doxycycline concentrations were measured using reverse phase high pressure liquid chromatography with ultraviolet detection.

Results: Doxycycline concentrations at all time points after t=0 were above the lower limit of quantification for the assay. Plasma concentrations of doxycycline were above 0.21 microg/ml at t=0.5 h. The mean+/-s.d. peak concentration (Cmax) of doxycycline in plasma was 0.37+/-0.22 microg/ml and time to peak concentration was 0.54+/-0.19 h. Synovial fluid concentrations of doxycycline were above 0.12 microg/ml 1 h after drug administration. The mean Cmax of doxycycline in the synovial fluid was 0.27+/-0.10 microg/ml. The penetration factor of doxycycline from plasma into synovial fluid, as determined by a ratio of the area-under-the-curve for synovial fluid:plasma during the sampling period, was 4.6.

Potential relevance: Orally administered doxycycline distributes easily into synovial fluid with a penetration factor of 4.6. Terminal half-life of the drug in synovial fluid was longer than in the plasma, indicating possible accumulation in this compartment. Further in vivo studies are warranted to define a medication protocol prior to routine clinical use of doxycycline for the treatment of OA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / analysis
  • Anti-Bacterial Agents / blood*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Area Under Curve
  • Dose-Response Relationship, Drug
  • Doxycycline / administration & dosage
  • Doxycycline / analysis
  • Doxycycline / blood*
  • Doxycycline / pharmacokinetics*
  • Half-Life
  • Horses*
  • Synovial Fluid / chemistry*


  • Anti-Bacterial Agents
  • Doxycycline