Pharmacokinetics, pharmacodynamics, and local tolerance at injection site of penicillin and gentamicin administered by intravenous regional limb perfusion in standing horses: comparison between weightbearing and flexed limbs.
Abstract: Intravenous regional limb perfusion (IVRLP) of antibiotics is a therapeutic method used to treat distal limb infections in horses. The objectives of this study were to determine the pharmacokinetic parameters and tolerance of sodium benzylpenicillin (NaBP) administered via IVRLP; to compare the feasibility, tolerance, and efficacy of performing IVRLP on a flexed limb versus a weightbearing limb; and to predict the efficacy of IVRLP using gentamicin or NaBP. A prospective crossover study was conducted with six horses, each undergoing four phases of antibiotic infusion (gentamicin at 2.2 mg/kg vs. NaBP at 7,333 IU/kg of BP) and limb positioning (weightbearing vs. flexed). Each antibiotic administration was followed by serial synovial and blood sampling to assess antibiotic concentrations. Inflammation and sensitivity to palpation were evaluated at both the injection site and the sampled joint. A pharmacokinetic/pharmacodynamic analysis was carried out to predict the efficacy of IVRLP by estimating area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) index values for various minimum inhibitory concentrations (MICs). Results: High synovial concentrations of NaBP and gentamicin were achieved, with notable variability between horses. NaBP IVRLP was well tolerated, although cephalic vein inflammation scores were significantly higher following NaBP infusion than gentamicin (p = 3.4 × 10). For all horses and both antibiotics, synovial antibiotic exposures were significantly greater in weightbearing limbs than in flexed limbs (p = 0.04 and 0.02 for NaBP and gentamicin, respectively). Cephalic vein inflammation scores were also significantly lower in weightbearing limbs than in flexed limbs (p = 2.5 × 10). In terms of predicted efficacy, a daily dose of 2.2 mg/kg gentamicin should be adequate to treat synovial infections involving Escherichia coli or Staphylococcus aureus, including resistant strains. For NaBP, a daily or every-other-day dose of 7,333 IU/kg of BP should be adequate to treat infections caused by Streptococcus equi and sensitive Staphylococcus aureus. Conclusions: These findings suggest that daily IVRLP with NaBP (7,333 IU/kg of BP) could be an effective treatment for distal limb infections caused by susceptible bacteria with a MIC of ≤ 2 µg/mL, with only mild local inflammation at the injection site. IVRLP with 2.2 mg/kg gentamicin appears effective for treating infections involving susceptible bacteria with an MIC of ≤ 16 µg/mL. Performing IVRLP on a weightbearing limb resulted in higher antibiotic exposure in the metacarpophalangeal joint and better tolerance than the flexed limb method.
© 2025. The Author(s).
Publication Date: 2025-11-07 PubMed ID: 41204239PubMed Central: PMC12595851DOI: 10.1186/s12917-025-04936-0Google Scholar: Lookup
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- Journal Article
- Comparative Study
Cite This Article
APA
Guillot M, Mespoulhes-Rivière C, Bousquet-Mélou A, Lacroix MZ, Roques BB, Lallemand EA.
(2025).
Pharmacokinetics, pharmacodynamics, and local tolerance at injection site of penicillin and gentamicin administered by intravenous regional limb perfusion in standing horses: comparison between weightbearing and flexed limbs.
BMC Vet Res, 21(1), 650.
https://doi.org/10.1186/s12917-025-04936-0 Publication
Researcher Affiliations
- Ecole Nationale Vétérinaire d'Alfort, CHUV-Equidés, Maisons-Alfort, France.
- Ecole Nationale Vétérinaire d'Alfort, ACAP3, Goustranville, F-14430, France.
- Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort, F-94700, France.
- INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
- INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
- INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
- INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France. elodie.lallemand@envt.fr.
MeSH Terms
- Animals
- Horses
- Gentamicins / pharmacokinetics
- Gentamicins / administration & dosage
- Gentamicins / pharmacology
- Gentamicins / adverse effects
- Anti-Bacterial Agents / pharmacokinetics
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / pharmacology
- Anti-Bacterial Agents / adverse effects
- Male
- Cross-Over Studies
- Female
- Prospective Studies
- Penicillin G / pharmacokinetics
- Penicillin G / administration & dosage
- Penicillin G / pharmacology
- Microbial Sensitivity Tests / veterinary
- Horse Diseases / drug therapy
- Extremities
Conflict of Interest Statement
Declarations. Ethics approval and consent to participate: This study follows national and institutional guidelines for the humane treatment of animals and complies with relevant legislation in France. It was approved by the local ethics committee, Comité d’Éthique ComEth ANSES/ENVA/UPEC (Comité d’éthique Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail / École Nationale Vétérinaire d’Alfort / Université Paris-Est Créteil), as well as by the national institutional animal care and use committees (Ministère de l’Enseignement Supérieur et de la Recherche, APAFIS #34714-202201142131762 v5). The horses were privately owned by an individual who provided informed consent for their participation in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Consent to participate: Not applicable.
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