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American journal of veterinary research2006; 67(10); 1687-1695; doi: 10.2460/ajvr.67.10.1687

Pharmacokinetics and pharmacodynamics of enrofloxacin and a low dose of amikacin administered via regional intravenous limb perfusion in standing horses.

Abstract: To evaluate the pharmacokinetic-pharmacodynamic parameters of enrofloxacin and a low dose of amikacin administered via regional IV limb perfusion (RILP) in standing horses. Methods: 14 adult horses. Methods: Standing horses (7 horses/group) received either enrofloxacin (1.5 mg/kg) or amikacin (250 mg) via RILP (involving tourniquet application) in 1 forelimb. Samples of interstitial fluid (collected via implanted capillary ultrafiltration devices) from the bone marrow (BMIF) of the third metacarpal bone and overlying subcutaneous tissues (STIF), blood, and synovial fluid of the radiocarpal joint were collected prior to (time 0) and at intervals after tourniquet release for determination of drug concentrations. For pharmacokinetic-pharmacodynamic analyses, minimum inhibitory concentrations (MICs) of 16 microg/mL (amikacin) and 0.5 microg/mL (enrofloxacin) were applied. Results: After RILP with enrofloxacin, 3 horses developed vasculitis. The highest synovial fluid concentrations of enrofloxacin and amikacin were detected at time 0; median values (range) were 13.22 microg/mL (0.254 to 167.9 microg/mL) and 26.2 microg/mL (5.78 to 50.0 microg/mL), respectively. Enrofloxacin concentrations exceeded MIC for approximately 24 hours in STIF and synovial fluid and for 36 hours in BMIF. After perfusion of amikacin, concentrations greater than the MIC were not detected in any samples. Effective therapeutic concentrations of enrofloxacin were attained in all samples. Conclusions: In horses with orthopedic infections, RILP of enrofloxacin (1.5 mg/kg) should be considered as a treatment option. However, care must be taken during administration. A dose of amikacin > 250 mg is recommended to attain effective tissue concentrations via RILP in standing horses.
Publication Date: 2006-10-04 PubMed ID: 17014317DOI: 10.2460/ajvr.67.10.1687Google Scholar: Lookup
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  • Clinical Trial
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research evaluates the effects and efficacy of administering enrofloxacin and a low dosage of amikacin to horses through a method called regional IV limb perfusion (RILP). Results indicate that enrofloxacin was more effective, maintaining inhibitory concentrations for up to 36 hours in certain tissues, suggesting its potential use for treating orthopedic infections. Amikacin, however, didn’t reach effective tissue concentrations, indicating a need for a higher dosage.

Study Design and Methods

  • The study focused on the effects of enrofloxacin (1.5 mg/kg) and amikacin (250 mg), administered to two groups of seven standing horses each, through a procedure known as regional IV limb perfusion (RILP).
  • This procedure involved applying a tourniquet to one forelimb of each horse, followed by the relevant drug administration.
  • Interstitial fluid samples from the bone marrow (BMIF) of the third metacarpal bone, local subcutaneous tissues (STIF), blood, and synovial fluid of the radiocarpal joint were collected before (at time 0) and at regular intervals after the tourniquet’s release.
  • These samples were then analyzed to determine drug concentrations.

Pharmacokinetic-Pharmacodynamic Analyses

  • The minimum inhibitory concentrations (MICs) of the drugs were set at 16 microg/mL for amikacin and 0.5 microg/mL for enrofloxacin.
  • Enrofloxacin and amikacin concentrations in synovial fluid were highest immediately after the tourniquet release; median values were 13.22 microg/mL and 26.2 microg/mL, respectively.
  • Enrofloxacin maintained effective concentrations in STIF and synovial fluid for around 24 hours and in BMIF for 36 hours.
  • No effective concentrations of amikacin that exceeded the MIC were detected in any of the samples.

Results and Recommendations

  • Three horses developed vasculitis after being administered enrofloxacin through RILP.
  • The findings confirmed that therapeutic concentrations of enrofloxacin were achieved in all samples, making it a viable treatment option for horses with orthopedic infections.
  • However, due to the risk of vasculitis, care must be taken when administering the drug.
  • The study also indicated that amikacin at the given dose (250 mg) didn’t reach effective tissue concentrations, suggesting a need for higher dosages to achieve therapeutic effects.

Cite This Article

APA
Parra-Sanchez A, Lugo J, Boothe DM, Gaughan EM, Hanson RR, Duran S, Belknap JK. (2006). Pharmacokinetics and pharmacodynamics of enrofloxacin and a low dose of amikacin administered via regional intravenous limb perfusion in standing horses. Am J Vet Res, 67(10), 1687-1695. https://doi.org/10.2460/ajvr.67.10.1687

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 67
Issue: 10
Pages: 1687-1695

Researcher Affiliations

Parra-Sanchez, Alberto
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
Lugo, Joel
    Boothe, Dawn M
      Gaughan, Earl M
        Hanson, R Reid
          Duran, Sue
            Belknap, James K

              MeSH Terms

              • Amikacin / administration & dosage
              • Amikacin / pharmacokinetics
              • Animals
              • Anti-Bacterial Agents / administration & dosage
              • Anti-Bacterial Agents / pharmacokinetics
              • Area Under Curve
              • Bone Marrow / metabolism
              • Enrofloxacin
              • Fluoroquinolones / pharmacokinetics
              • Forelimb
              • Horses / metabolism
              • Microbial Sensitivity Tests
              • Random Allocation
              • Synovial Fluid / metabolism
              • Tissue Distribution

              Citations

              This article has been cited 8 times.
              1. Khairullah AR, Sudjarwo SA, Effendi MH, Ramandinianto SC, Widodo A, Riwu KHP. A review of horses as a source of spreading livestock-associated methicillin-resistant Staphylococcus aureus to human health. Vet World 2022 Aug;15(8):1906-1915.
              2. 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
              3. 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.
                doi: 10.3389/fvets.2021.629627pubmed: 33842571google scholar: lookup
              4. Celani G, Tulini SMR, Montesano C, Zezza D, Sergi M, Varasano V, Mortellaro CM, Compagnone D, Amorena M, Petrizzi L. Pharmacokinetics of marbofloxacin administered via intravenous regional limb perfusion in dairy cows: evaluation of two different tourniquets. Vet Rec Open 2017;4(1):e000227.
                doi: 10.1136/vetreco-2017-000227pubmed: 29018533google scholar: lookup
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                doi: 10.1186/s12917-015-0472-zpubmed: 26174778google scholar: lookup
              6. Hunter BG, Duesterdieck-Zellmer KF, Larson MK. Tiludronate concentrations and cytologic findings in synovial fluid after intravenous regional limb perfusion with tiludronate in horses. PeerJ 2015;3:e889.
                doi: 10.7717/peerj.889pubmed: 25945303google scholar: lookup
              7. Hyde RM, Lynch TM, Clark CK, Slone DE, Hughes FE. The influence of perfusate volume on antimicrobial concentration in synovial fluid following intravenous regional limb perfusion in the standing horse. Can Vet J 2013 Apr;54(4):363-7.
                pubmed: 24082163
              8. Xu L, Wang H, Yang X, Lu L. Integrated pharmacokinetics/pharmacodynamics parameters-based dosing guidelines of enrofloxacin in grass carp Ctenopharyngodon idella to minimize selection of drug resistance. BMC Vet Res 2013 Jun 25;9:126.
                doi: 10.1186/1746-6148-9-126pubmed: 23800340google scholar: lookup