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Home / Equine Research Bank / Can J Vet Res / Pharmacokinetics of a combination of amikacin sulfate and pe...
Canadian journal of veterinary research = Revue canadienne de recherche veterinaire2016; 80(3); 230-235;

Pharmacokinetics of a combination of amikacin sulfate and penicillin G sodium for intravenous regional limb perfusion in adult horses.

Abstract: The aim of this study was to determine the pharmacokinetics of amikacin and penicillin G sodium when administered in combination as an intravenous regional limb perfusion (IVRLP) to horses. Seven healthy adult horses underwent an IVRLP in the cephalic vein with 2 g of amikacin sulfate and 10 mill IU of penicillin G sodium diluted to 60 mL in 0.9% saline. A pneumatic tourniquet set at 450 mmHg was left in place for 30 min. Synovial fluid was collected from the metacarpophalangeal joint 35 min and 2, 6, 12, and 24 h after infusion of the antimicrobials. Concentrations of amikacin and penicillin in synovial fluid were quantitated by liquid chromatography tandem-mass spectrometry analysis. Therapeutic concentrations of amikacin and penicillin for equine-susceptible pathogens were achieved in the synovial fluid. Maximum synovial concentrations (Cmax) (mean ± SE) for amikacin and penicillin were 132 ± 33 μg/mL and 8474 ± 5710 ng/mL, respectively. Only 3 horses had detectable levels of penicillin at 6 h and 1 at the 12 h sample. The combination of amikacin with penicillin G sodium via IVDLP resulted in reported therapeutic concentrations of both antibiotics in the synovial fluid. The Cmax:MIC (minimum inhibitory concentration) ratio for amikacin was 8:1 and Time > MIC for penicillin was 6 h. At 24 h, the mean concentration of amikacin was still above 4 μg/mL. Terminal elimination rate constants (T1/2 lambdaz) were 13.6 h and 2.8 h for amikacin and penicillin, respectively. The use of IVDLP with penicillin may therefore not be practical as rapid clearance of penicillin from the synovial fluid requires frequent perfusions to maintain acceptable therapeutic concentrations. L’objectif de la présente étude était de déterminer la pharmacocinétique de l’amikacine et de la pénicilline G sodique lorsqu’administrées en combinaison par perfusion intraveineuse régionale d’un membre (PIVRM) à des chevaux. Sept chevaux adultes ont reçu une PIVRM dans la veine céphalique avec 2 g de sulfate d’amikacine et 10 millions d’UI de pénicilline G sodique dilués dans 60 mL de saline 0,9 %. Un tourniquet pneumatique réglé à 450 mmHg a été laissé en place pour 30 min. Du liquide synovial a été récolté de l’articulation métacarpo-phalangienne 35 min, 2, 6, 12, et 24 h après l’infusion des antimicrobiens. Les concentrations d’amikacine et de pénicilline dans le liquide synovial furent mesurées par spectrométrie de masse en tandem avec la chromatographie en phase liquide. Les concentrations thérapeutiques d’amikacine et de pénicilline pour des agents pathogènes équins sensibles ont été atteintes dans le liquide synovial. Les concentrations synoviales maximales (Cmax) [moyenne ± écart-type (EC)] pour l’amikacine et la pénicilline étaient de 132 ± 33 μg/mL et 8474 ± 5710 ng/mL, respectivement. Seulement 3 chevaux avaient des quantités détectables de pénicilline à 6 h et un seul pour l’échantillon de 12 h. La combinaison d’amikacine et de pénicilline G sodique via PIVRM a permis de rapporter des concentrations thérapeutiques des deux antibiotiques dans le liquide synovial. Le ratio Cmax-CMI (concentration minimale inhibitrice) pour l’amikacine était de 8:1 et la période de Temps > CMI pour la pénicilline était de 6 h. À 24 h, la concentration moyenne d’amikacine était toujours supérieure à 4 μg/mL. Les constantes du taux d’élimination terminal (T1/2 lambdaz) étaient 13,6 h et 2,8 h pour l’amikacine et la pénicilline, respectivement. L’utilisation de PIVRM avec la pénicilline ne serait ainsi pas pratique étant donné que la clairance rapide de la pénicilline à partir du liquide synovial requière des perfusions fréquentes pour maintenir des concentrations thérapeutiques acceptables.(Traduit par Docteur Serge Messier).
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Publication Date: 2016-07-14 PubMed ID: 27408337PubMed Central: PMC4924558
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study evaluates the effectiveness of intravenous regional limb perfusion (IVRLP) therapy with a combined amikacin and penicillin in horses. It found that while this method achieved therapeutic levels of both antibiotics in the synovial fluid, rapid clearance of penicillin necessitates frequent perfusions to keep therapeutic concentrations.

Objective and Methodology of the Study

  • The research aimed to understand the pharmacokinetics ( how the body processes a drug) of amikacin and penicillin G sodium when administered through intravenous regional limb perfusion (IVRLP) in horses. IVRLP is a method used to deliver high concentrations of antibiotics directly to a localized area.
  • Seven healthy adult horses were used for the experiment where they were administered a combination of 2g amikacin sulfate and 10 million IU of penicillin G sodium via an IVRLP in their cephalic vein. A pneumatic tourniquet set at 450 mmHg was left in place for 30 min to restrict the spread of the drugs.
  • Samples of synovial fluid (fluid around the joints) were collected at specific intervals post the infusion to measure the antibiotic concentrations. The measuring was done using liquid chromatography tandem-mass spectrometry analysis.

Results of the Study

  • Therapeutic concentrations of amikacin and penicillin for pathogens susceptible to these antibiotics were achieved in the synovial fluid.
  • Maximum synovial concentrations (Cmax) for amikacin and penicillin were 132 ± 33 μg/mL and 8474 ± 5710 ng/mL, respectively.
  • Penicillin was detected in only three horses at the 6-hour mark, and in only one horse at the 12-hour sample collection.
  • The Cmax:MIC (minimum inhibitory concentration) ratio for amikacin was 8:1, hinting at its effective concentration. Time > MIC for penicillin was 6 hours, indicating that penicillin stayed at a therapeutic concentration for 6 hours.
  • Terminal elimination rate constants (indicating how long the drug stayed in system) were 13.6 hours for amikacin and 2.8 hours for penicillin.

Implications and Conclusion

  • The IVRLP method produced therapeutic concentrations of both amikacin and penicillin in the synovial fluid. Though this indicates the method’s effectiveness, penicillin’s rapid clearance from synovial fluid might necessitate frequent drug infusions to maintain its therapeutic concentration.
  • This could mean that the use of penicillin in IVRLP might be impractical due to the need for frequent infusions.
  • Therefore, the choice of antibiotic to be used in this kind of perfusion therapy might need to be reconsidered, especially for longer-term treatment.

Cite This Article

APA
Nieto JE, Trela J, Stanley SD, Yamout S, Snyder JR. (2016). Pharmacokinetics of a combination of amikacin sulfate and penicillin G sodium for intravenous regional limb perfusion in adult horses. Can J Vet Res, 80(3), 230-235.

Publication

Canadian journal of veterinary research = Revue canadienne de recherche veterinaire
ISSN: 1928-9022
NlmUniqueID: 8607793
Country: Canada
Language: English
Volume: 80
Issue: 3
Pages: 230-235

Researcher Affiliations

Nieto, Jorge E
  • Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.
Trela, Jan
  • Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.
Stanley, Scott D
  • Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.
Yamout, Sawsan
  • Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.
Snyder, Jack R
  • Department of Surgery and Radiological Sciences (Nieto, Trela, Yamout, Snyder) and K.L. Maddy Equine Analytical Chemistry Laboratory (Stanley), School of Veterinary Medicine, University of California, Davis, California 95616, USA.

MeSH Terms

  • Administration, Intravenous
  • Amikacin / administration & dosage
  • Amikacin / chemistry
  • Amikacin / pharmacokinetics
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Area Under Curve
  • Drug Therapy, Combination
  • Female
  • Half-Life
  • Horses / metabolism
  • Male
  • Penicillin G / administration & dosage
  • Penicillin G / chemistry
  • Penicillin G / pharmacokinetics
  • Perfusion / veterinary
  • Synovial Fluid / chemistry
  • Tissue Distribution

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Citations

This article has been cited 5 times.
  1. Mosichuk AP, Smith JS, Tatarniuk DM, Troy JR, Kreuder AJ. Meropenem Administered via Intravenous Regional Limb Perfusion for Orthopedic Sepsis in Horses: A Clinical Retrospective Study. Front Vet Sci 2021;8:629627.
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  2. Gilbertie JM, Schnabel LV, Hickok NJ, Jacob ME, Conlon BP, Shapiro IM, Parvizi J, Schaer TP. Equine or porcine synovial fluid as a novel ex vivo model for the study of bacterial free-floating biofilms that form in human joint infections. PLoS One 2019;14(8):e0221012.
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  3. Dahan R, Oreff GL, Tatz AJ, Raz T, Britzi M, Kelmer G. Pharmacokinetics of regional limb perfusion using a combination of amikacin and penicillin in standing horses. Can Vet J 2019 Mar;60(3):294-299.
    pubmed: 30872853
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  5. Khatibzadeh SM, Dahlgren LA, Caswell CC, Ducker WA, Werre SR, Bogers SH. Equine bone marrow-derived mesenchymal stromal cells reduce established S. aureus and E. coli biofilm matrix in vitro. PLoS One 2024;19(10):e0312917.
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