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Vet Comp Orthop Traumatol 2021; 34(04): 287-293
DOI: 10.1055/s-0041-1726083
Original Research

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

Kajsa Gustafsson 
1   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
,
Amos J. Tatz
1   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
,
Roee Dahan
1   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
,
Malka Britzi
2   National Residue Control Laboratory, Kimron Veterinary Institute, Beit Dagan, Israel
,
Stefan Soback
2   National Residue Control Laboratory, Kimron Veterinary Institute, Beit Dagan, Israel
,
Wiessam Abu Ahmad
3   Braun School of Public Health and Community Medicine, Hebrew University-Hadassah Braun School of Public Health and Community Medicine, Jerusalem, Israel
,
Hagar Prince
1   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
,
Gal Kelmer
1   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
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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 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.

Keywords

metronidazole - equine - intravenous regional limb perfusion - synovial fluid - distal interphalangeal joint

Note

The study was presented in part at the ECVS and ACVS annual scientific meetings 2019.


Author's Contributions

K.G. contributed to all parts of the study. A.J.T., R.D., H.P. and G.K. contributed to the conception of study, study design, acquisition of data and preparation and approval of the manuscript. M.B. and S.S. contributed to the acquisition of data, data analysis and interpretation and preparation and approval of the manuscript. W.A.A. contributed to data analysis ad interpretation and preparation and approval of the final manuscript.


Supplementary Material



Publication History

Received: 13 March 2020

Accepted: 26 January 2021

Article published online:
12 May 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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