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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, RESULTS. Meshes: Administration, Oral, Animals, Anti-Bacterial Agents, Area Under Curve, Dose-Response Relationship, Drug, Doxycycline, Half-Life, Horses, Synovial Fluid.
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Does orally administered doxycycline accumulate in synovial fluid compared to plasma? Context: 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. To determine the concentration of doxycycline in synovial fluid following oral, low-dose administration. 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. 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.
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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. Final Decision: yes