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Veterinary and comparative orthopaedics and traumatology : V.C.O.T2021; 34(4); 287-293; doi: 10.1055/s-0041-1726083

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

Abstract:  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. Conclusions:  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.
Publication Date: 2021-05-12 PubMed ID: 33979876DOI: 10.1055/s-0041-1726083Google Scholar: Lookup
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  • Journal Article

Summary

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The research paper tries to evaluate the concentration of antibiotic metronidazole in a specific joint of a horse’s forelimb after administering it through intravenous regional limb perfusion. The article recognizes the immediate boost in metronidazole concentration, but notes it quickly drops below a useful level for combating potential pathogens, hinting that sole therapy using this method may prove ineffective for treating certain infections.

Objective & Methodology

  • The study’s goal was to evaluate the level or concentration of the antibiotic ‘metronidazole’ in the distal interphalangeal joint (DIPJ) of the forelimb in horses when applied through intravenous regional limb perfusion (IVRLP). IVRLP is a technique where a drug is administered into a specific area of the body, in this case, a horse’s limb, for targeted action.
  • The research involved 11 healthy horses that were treated with a tourniquet on the forearm (antebrachium) before injecting 500 mg of metronidazole diluted in a saline solution via IVRLP.
  • Samples of synovial fluid, found in the joints, were taken from the DIPJ before administration and at several intervals post-administration—0.25, 0.5, 2, 12, and 24 hours. Blood samples were also collected during the same period for serum analysis, allowing the researchers to track the metronidazole levels.
  • The concentrations were then determined using liquid chromatography/tandem mass spectrometry – a reliable method to measure concentrations of substances at the molecular level.

Results

  • Of the 11 horses, four were excluded because of inadequate synovial fluid and incomplete tourniquet application.
  • At 0.5 hours, it was found that a high concentration of metronidazole was present in the synovial fluid. However, the concentrations quickly dropped and were significantly different from pre-perfusion levels at 0.25 and 0.5 hours post-administration.
  • The serum analysis also mirrored the synovial fluid results; high levels initially, followed by a quick drop in concentration.

Conclusions and Future Implications

  • From this study, it’s been observed that administering metronidazole via IVRLP can result in high, but quickly decreasing concentrations in the synovial fluid. The levels fell abruptly under the minimum inhibitory concentration, a parameter indicating the lowest level of an antibiotic needed to inhibit the growth of bacteria.
  • Thus, the effectiveness of using metronidazole through IVRLP as the only therapy for anaerobic infections in the synovial structures of a horse’s distal limb remains uncertain based on this study’s findings.
  • The paper emphasizes that the results serve as a fundamental research for future detailed clinical trials. This means further studies are required to conclude the effectiveness of this process.

Cite This Article

APA
Gustafsson K, Tatz AJ, Dahan R, Britzi M, Soback S, Ahmad WA, Prince H, Kelmer G. (2021). The Concentration of Metronidazole in the Distal Interphalangeal Joint following Intravenous Regional Limb Perfusion via the Cephalic Vein in Standing Horses. Vet Comp Orthop Traumatol, 34(4), 287-293. https://doi.org/10.1055/s-0041-1726083

Publication

ISSN: 2567-6911
NlmUniqueID: 8906319
Country: Germany
Language: English
Volume: 34
Issue: 4
Pages: 287-293

Researcher Affiliations

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

MeSH Terms

  • Administration, Intravenous / veterinary
  • Amikacin
  • Animals
  • Anti-Bacterial Agents
  • Forelimb
  • Horses
  • Metronidazole
  • Perfusion / veterinary
  • Synovial Fluid

Conflict of Interest Statement

None declared.

Citations

This article has been cited 1 times.
  1. Redding LE, Elzer EJ, Ortved KF. Effects of regional limb perfusion technique on concentrations of antibiotic achieved at the target site: A meta-analysis. PLoS One 2022;17(4):e0265971.
    doi: 10.1371/journal.pone.0265971pubmed: 35363825google scholar: lookup