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Home » Archive » 2021 » Veterinary Session

Veterinary session

PK/PD analysis in porcine health
Mag Patrik - year 6
University of Veterinary Medicine Budapest, Department of Pharmacology and Toxicology
Supervisor: Dr. Zoltán Somogyi

Abstract:

Florfenicol is an antibacterial agent, belonging to the phenicol group, which, due to its structural changes, has much higher in vitro activity when compared to the other two members of the group: thiamphenicol and chloramphenicol. The aim of our study was to demonstrate that florfenicol may be a possible indication for arthritis caused by Streptococcus suis in pigs.

In our study, we investigated the pharmacokinetic properties of florfenicol in 5 pigs. We determined the dose of florfenicol according to the directions for use for commercially available solution for injection (15 mg/kgbw) and it was administered intramuscularly, deep into the neck muscle. Blind samples (blood and synovial fluid) were taken from each animal prior to drug administration. After the drug administration, blood was drawn at the following times: 10, 20, 30, 40, 50, 60 minutes, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, and 72 hours, while synovial fluid samples were taken after 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours. This was followed by determination of the concentration of florfenicol in the samples by liquid chromatography-mass spectrometry (LC-MS/MS) in multiple reaction monitoring (MRM) mode, which provided adequate sensitivity and selectivity.

Our results were as follows: florfenicol reached peak plasma concentrations (Cmax) in the plasma (Cmax=3.005 µg/ml) 3 hours after dosing (tmax) and in the synovial fluid (Cmax=2.247 µg/ml) 2 hours after dosing (tmax). The half-life (t1/2) in plasma was 22.737 hours, while in synovial fluid it was 29.358 hours. Area under the curve for 24 hours (AUC0-24) was 49.162 μg/ml*h in plasma and 28.536 μg/ml*h in synovial fluid.

As for the second part of our research, minimum inhibitory concentration (MIC) values of florfenicol – as a pharmacodynamic parameter – were determined in 45 S. suis strains isolated from clinical samples collected in Hungary. The MIC50 value for S. suis strains was 2.0 µg/ml, while the MIC90 value was 16.0 µg/ml. Furthermore, minimum bactericidal concentration (MBC) and mutation prevention concentration (MPC) were determined for a selected strain of Streptococcus suis serotype two. The MIC value of this strain was 0,5 µg/ml, MBC was 2.0 µg/ml and MPC was 1.0 µg/ml. PK/PD analysis has been performed considering T>MIC and AUC0-24/MIC ratios.



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