title: Orally administered doxycycline accumulates in synovial fluid compared to plasma.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: L V
authors.initials: LV
authors.lastname: Schnabel
authors.forename: M G
authors.initials: MG
authors.lastname: Papich
authors.forename: A E
authors.initials: AE
authors.lastname: Watts
authors.forename: L A
authors.initials: LA
authors.lastname: Fortier
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis / Q000097:blood* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000008:administration & dosage / Q000032:analysis / Q000097:blood* / Q000493:pharmacokinetics*; D006207:Half-Life; D006736:Horses; D013582:Synovial Fluid / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D004318:Doxycycline