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 0.5 hours and 500 mg of metronidazole diluted in physiologic saline solution to a total volume of 108 mL was administered by cephalic IVRLP. Synovial fluid samples were collected from the DIPJ before perfusion and at 0.25, 0.5, 2, 12 and 24 hours. 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 327 ± 208 µg/mL, and the t _max was 26 ± 7 minutes. Only the concentrations of metronidazole at time points 0.25 and 0.5 hours were significantly different (p < 0.001) from synovial concentration before perfusion. The serum C _max was 1.78 ± 0.93 µg/mL, and the t _max was 76 ± 52min.

Conclusion Metronidazole administered by IVRLP reached high concentrations in the synovial fluid at 0.5 hours. 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.

目的 本研究的目的是通过静脉区域肢体灌注（IVRLP）对站立的马施用甲硝唑后测定胸肢远端指间关节（DIPJ）中甲硝唑的浓度。

方法 11 匹健康马在前臂近端应用宽橡胶止血带 0.5 小时，并通过头侧 IVRLP 给予 500 mg 用生理盐水溶液稀释至总体积 108 mL 的甲硝唑。在灌注前和在 0.25、0.5、2、12 和 24 小时从 DIPJ 收集滑液样品。在同一时间点采集血样用于血清分析。甲硝唑的浓度通过液相色谱/串联质谱法测定。

结果 由于滑液浓度低且未完成止血带应用时间，四匹马被排除在外。滑液中的C _max为 327 ± 208 µg/mL，t _max为 26 ± 7 分钟。只有在时间点 0.25 和 0.5 小时的甲硝唑浓度与 灌注前滑膜浓度有显着差异 ( p < 0.001)。血清C _max为 1.78 ± 0.93 µg/mL，t _max为 76 ± 52 分钟。

结论 IVRLP 给药的甲硝唑在 0.5 小时时在滑液中达到高浓度。然而，浓度迅速下降到低于潜在目标病原体的最低抑制浓度。药代动力学研究无法确定通过 IVRLP 施用的甲硝唑作为单独治疗肢体远端滑膜结构厌氧菌感染的有效性。然而，本研究可作为未来精心规划的临床试验的基础。