头静脉静脉区域性肢体灌注后站立马匹的远侧指间关节中甲硝唑的浓度。

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

机构信息

Department of Large Animal Medicine and Surgery, Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, the Hebrew University of Jerusalem, Rehovot, Israel.

National Residue Control Laboratory, Kimron Veterinary Institute, Beit Dagan, Israel.

出版信息

Vet Comp Orthop Traumatol. 2021 Jul;34(4):287-293. doi: 10.1055/s-0041-1726083. Epub 2021 May 12.

DOI:10.1055/s-0041-1726083

PMID:33979876

Abstract

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 in the synovial fluid was 327 ± 208 µg/mL, and the was 26 ± 7 minutes. Only the concentrations of metronidazole at time points 0.25 and 0.5 hours were significantly different ( < 0.001) from synovial concentration before perfusion. The serum was 1.78 ± 0.93 µg/mL, and the 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.

摘要

目的

本研究旨在通过静脉区域性肢体灌注（IVRLP）向站立马匹的四肢给药，确定替硝唑在胸部肢体的远节指间关节（DIPJ）中的浓度。

方法

11 匹健康的马在前臂近端应用宽橡胶止血带 0.5 小时，将 500mg 替硝唑稀释在生理盐水中，总容量为 108ml，通过头静脉 IVRLP 给药。在灌注前和 0.25、0.5、2、12 和 24 小时从 DIPJ 采集滑液样本。同时在相同时间点采集血液样本进行血清分析。通过液相色谱/串联质谱法测定替硝唑浓度。

结果

由于滑液浓度低且未完成整个止血带应用时间，有 4 匹马被排除在外。关节液中的替硝唑浓度为 327 ± 208 µg/ml，半衰期为 26 ± 7 分钟。只有在 0.25 和 0.5 小时这两个时间点的替硝唑浓度与灌注前的关节液浓度有显著差异（<0.001）。血清替硝唑浓度为 1.78 ± 0.93 µg/ml，半衰期为 76 ± 52 分钟。