The Concentration of Metronidazole in the Distal Interphalangeal Joint following Intravenous Regional Limb Perfusion via the Cephalic Vein in Standing Horses

Objective The aim of this study was to determine the concentration of metronidazole in the distal interphalangeal joint (DIPJ) of the thoracic limb after administering metronidazole to standing horses by intravenous regional limb perfusion (IVRLP). Methods Eleven healthy horses had a wide rubber tourniquet applied to the proximal aspect of the antebrachium for 0.5hours and 500mg of metronidazole diluted in physiologic saline solution to a total volume of 108mL was administered by cephalic IVRLP. Synovial fluid samples were collected from the DIPJ before perfusion and at 0.25, 0.5, 2, 12 and 24hours. Blood samples were obtained at the same time points for serum analysis. Concentrations of metronidazole were determined by liquid chromatography/tandem mass spectrometry. Results Four horses were excluded due to low synovial fluid concentrations and not completing the full tourniquet application time. The C-max in the synovial fluid was 327208 mu g/mL, and the t(max) was 26 +/- 7minutes. Only the concentrations of metronidazole at time points 0.25 and 0.5hours were significantly different ( p <0.001) from synovial concentration before perfusion. The serum C-max was 1.78<plus/minus>0.93 mu g/mL, and the t(max) was 76 +/- 52min. Conclusion Metronidazole administered by IVRLP reached high concentrations in the synovial fluid at 0.5hours. However, the concentrations rapidly decreased below the minimum inhibitory concentration of potential target pathogens. Effectiveness of metronidazole administered by IVRLP as a sole therapy against anaerobic infections of synovial structures of the distal limb cannot be determined by a pharmacokinetic study. However, the present study serves as the basis for future carefully planned clinical trials.