Pharmacokinetics and Pharmacodynamics of Florfenicol in Plasma and Synovial Fluid of Pigs at a Dose of 30 mg/kgbw Following Intramuscular Administration
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Published:2023-04-14
Issue:4
Volume:12
Page:758
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ISSN:2079-6382
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Container-title:Antibiotics
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language:en
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Short-container-title:Antibiotics
Author:
Somogyi Zoltán12, Mag Patrik12, Simon Réka1, Kerek Ádám12ORCID, Szabó Pál3ORCID, Albert Ervin45ORCID, Biksi Imre45, Jerzsele Ákos12ORCID
Affiliation:
1. Department of Pharmacology and Toxicology, University of Veterinary Medicine, 1078 Budapest, Hungary 2. National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health and Food Chain Safety, University of Veterinary Medicine, 1078 Budapest, Hungary 3. Research Center for Natural Sciences, Center for Structural Study, MS Metabolomics Laboratory, 1117 Budapest, Hungary 4. Department of Pathology, University of Veterinary Medicine Budapest, 2225 Üllő, Hungary 5. SCG Diagnostics Ltd., 2437 Délegyháza, Hungary
Abstract
A major problem of our time is the ever-increasing resistance to antimicrobial agents in bacterial populations. One of the most effective ways to prevent these problems is to target antibacterial therapies for specific diseases. In this study, we investigated the in vitro effectiveness of florfenicol against S. suis, which can cause severe arthritis and septicemia in swine herds. The pharmacokinetic and pharmacodynamic properties of florfenicol in porcine plasma and synovial fluid were determined. After a single intramuscular administration of florfenicol at 30 mg/kgbw, the AUC0–∞ was 164.45 ± 34.18 µg/mL × h and the maximum plasma concentration was 8.15 ± 3.11 µg/mL, which was reached in 1.40 ± 0.66 h, whereas, in the synovial fluid, these values were 64.57 ± 30.37 µg/mL × h, 4.51 ± 1.16 µg/mL and 1.75 ± 1.16 h, respectively. Based on the MIC values of the 73 S. suis isolates tested, the MIC50 and MIC90 values were 2 µg/mL and 8 µg/mL, respectively. We successfully implemented a killing–time curve in pig synovial fluid as a matrix. Based on our findings, the PK/PD breakpoints of the bacteriostatic (E = 0), bactericidal (E = −3) and eradication (E = −4) effects of florfenicol were determined and MIC thresholds were calculated, which are the guiding indicators for the treatment of these diseases. The AUC24h/MIC values for bacteriostatic, bactericidal and eradication effects were 22.22 h, 76.88 h and 141.74 h, respectively, in synovial fluid, and 22.42 h, 86.49 h and 161.76 h, respectively, in plasma. The critical MIC values of florfenicol against S. suis regarding bacteriostatic, bactericidal and eradication effects in pig synovial fluid were 2.91 ± 1.37 µg/mL, 0.84 ± 0.39 µg/mL and 0.46 ± 0.21 µg/mL, respectively. These values provide a basis for further studies on the use of florfenicol. Furthermore, our research highlights the importance of investigating the pharmacokinetic properties of antibacterial agents at the site of infection and the pharmacodynamic properties of these agents against different bacteria in different media.
Funder
Recovery and Resilience Facility National Recovery Fund budget estimate
Subject
Pharmacology (medical),Infectious Diseases,Microbiology (medical),General Pharmacology, Toxicology and Pharmaceutics,Biochemistry,Microbiology
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