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Predicted efficacy and tolerance of different dosage regimens of benzylpenicillin in horses based on a pharmacokinetic study with three IM formulations and one IV formulation.
Abstract: Benzylpenicillin (BP) is a first-line antibiotic in horses but there are discrepancies between manufacturers and literature recommendations regarding dosing regimen. Objectives of this study were to evaluate pharmacokinetics and local tolerance of four different formulations of BP in adult horses, and to suggest optimized dosing regimen according to the formulation. Unassigned: A cross-over design was used in 3 phases for the intramuscular injection of three different products: procaine BP alone, procaine BP/ benzathine BP combination or penethamate hydriodide were administered IM in the gluteal muscles of 6 horses for 3 days. Single IV administration of sodium BP was performed to the same horses with a dose of 22,000 IU BP/kg bwt 39 weeks after last IM injection. BP plasma concentrations were determined by UPLC assay coupled with mass spectrometry and a PK/PD analysis was conducted to predict the efficacy of various dosing regimens by estimating values of the fT>MIC index for different minimum inhibitory concentrations (MIC). Tolerance at the site of IM injection was monitored by creatine kinase activity quantified with a validated chemistry system and clinical scorings. Unassigned: Except one neurological reaction following one administration of penethamate hydriodide, the tolerance was good. Procaine BP alone, procaine BP/benzathine BP combination or penethamate hydriodide intramuscular administrations at a dosage of 22,000 IU BP/kg bwt q24h for 5 days would yield plasma concentrations that should be effective against bacteria with MIC of ≤0.256, 0.125 or 0.064 mg/L respectively. Of all the tested treatments, the use of a sodium BP by IV Constant Rate Infusion (CRI) for 10 hours a day was deemed to be the most efficient. All the formulations tested in this study are adequate to treat infections with susceptible .
Copyright © 2024 Ferran, Roques, Chapuis, Kuroda, Lacroix, Toutain, Bousquet-Melou and Lallemand.
Publication Date: 2024-05-31 PubMed ID: 38881781PubMed Central: PMC11176610DOI: 10.3389/fvets.2024.1409266Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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The research examines the effectiveness and tolerance of various dosage regimens of the antibiotic benzylpenicillin (BP) in horses. The study proposes an optimized dosing regimen based on different BP formulations, seeking to resolve existing inconsistencies in dosing recommendations from manufacturers and literature.
Methodology
- The research utilized a cross-over design spread over three phases, using intramuscular (IM) injections of three different forms of BP: procaine BP alone, a mix of procaine BP and benzathine BP, and penethamate hydriodide.
- The six horses involved in the study received these injections on their gluteal muscles over a three-day period.
- Additionally, the same group of horses received a single intravenous (IV) administration of sodium BP, which was injected 39 weeks after the final IM injection.
- The blood plasma levels of BP were observed using an Ultra Performance Liquid Chromatography (UPLC) assay linked with mass spectrometry, an analytical technique used to measure the mass within a sample.
- Pharmacokinetic/Pharmacodynamic (PK/PD) analysis was then carried out to estimate the effectiveness of different dosing regimens, calculated using the fT>MIC index values for various minimum inhibitory concentrations (MICs).
- The horses’ tolerance at the injection site was also assessed by determining the activity of the enzyme creatine kinase and various clinical scorings.
Results
- The research yielded notable findings about BP’s effectiveness and horse’s tolerance of different dosage methods.
- There was just one occurrence of a neurological reaction due to the injection of penethamate hydriodide. Otherwise, the horses’ tolerance of the treatments was good.
- A dosage of 22,000 IU BP/kg bwt q24h for five consecutive days for procure BP alone, procure BP/benzathine BP combination, or penethamate hydriodide produced blood plasma levels that should effectively combat bacteria with respective MICs of ≤0.256, 0.125, or 0.064 mg/L.
- A ten-hour daily dosage of sodium BP by IV Constant Rate Infusion (CRI) was identified as the most effective treatment of all the tested methods.
- All the tested formulations proved effective in treating infections with susceptible bacteria.
Conclusion
- The study provides important insights into the effectiveness and tolerance of varying dosages and formulations of BP in horses.
- It also contributes valuable data and suggestions towards optimizing the dosing regimens of this widely used antibiotic in treating equine infections.
Cite This Article
APA
Ferran AA, Roques BB, Chapuis L, Kuroda T, Lacroix MZ, Toutain PL, Bousquet-Melou A, Lallemand EA.
(2024).
Predicted efficacy and tolerance of different dosage regimens of benzylpenicillin in horses based on a pharmacokinetic study with three IM formulations and one IV formulation.
Front Vet Sci, 11, 1409266.
https://doi.org/10.3389/fvets.2024.1409266 Publication
Researcher Affiliations
- INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
- INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
- INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
- Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
- INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
- INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
- Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London, United Kingdom.
- INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
- INTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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