Students' Research Circle    
 
 
Call for papers
The conference
Veterinary Session
Veterinary Jury
Biology Session
Sponsors
Awards-list
Galleries
» Archive
2022
2021
2020
2019
2018
2017
2016
2015
2014
2013
2012
2011
2010
2009
2008
2007
2006
2005
2004
2003
2002
Regulations
Home » Archive

Archive

Pharmacokinetic properties of intramuscularly administered florfenicol in pig synovial fluid at the dose of 30 mg/kg and PK/PD integration against Streptococcus suis
Simon Réka - year 5
University of Veterinary Medicine Budapest, Department of Pharmacology and Toxicology
Supervisor: Dr. Zoltán Somogyi

Abstract:

Florfenicol is a low molecular weight drug from the phenicol group with a wide antibacterial spectrum, which has a bacteriostatic mode of action against both Gram-positiv and Gram-negative bacteria. It is excellently absorbed after intramuscular, subcutaneous and oral administration and similarly, it is excellently distributed throughout the body, so it can also cross special membranes. The primary goal of my research is to determine the pharmakokinetic properties of florfenicol administered intramuscularly in high doses (30 mg/kg) in pig synovial fluid and to investigate the importance of this method of application in the treatment of arthritis caused by Streptococcus suis.

The studeis were carried out with 8 Danbred pigs weighing 28.93 ± 3.64 kg, in with the dose of florfenicol was determined at 30 mg/kg instead of 15 mg/kg, using the intramuscular route of administration once, contrary to the description of the use of the approved preparations. In the animal phase of the experiment, plasma and synovial fluid samples were collected once before and at the following times after drug administration: 10, 20, 30, 40, 50 and 60 minutes and 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, 72 hours for the plasma and 1, 2, 3, 4, 8, 12, 24, 48, 72 hours for the synovial fluid respectively. The concentration in the plasma and the synovial fluid was determined usin liquid chromatography-mass spectometry (LC-MS/MS) in multiple reaction tracking mode (MRM), which ensured sufficient sensitivity and selectivity of the method.

Florfenicol reached its maximum concentration in plasma at 1.75± 0.66 hours (tmax) after administration (cmax= 8.15±3.11 µg/ml) while in the synovial fluid the tmax was 1.75±1.16 hours (cmax=4.51 ±1.16 µg/ml). In the plasma the half-life (t1/2) was 17.93±11.68 hours, while in the synovial fluid it wqas 12.27±7.45 hours. The area under the curve projected over 24 hours (AUC24h) is 104.77±21.56 µg/ml*h in the plasma and 44.12±17.23 µg/ml*h in the synovial fluid.

Following the pharmacokinetic studies, the sensitivity of 73 Streptococcus suis isolates of porcine origin to florfenicol was determined using a microdilution method, resulting in minimum inhibitory concentration (MIC) values. Based on the MIC values, I calculated the values of MIC50 (2 µg/ml) and MIC90 (8 µg/ml). Using pharmacokinetic and pharmacodynamic data, %T>MIC and AUC24h/MIC were performed from the PK/PD integrations according to which, compared to S. suis strains with a MIC of 2 µg/ml or less for florfenicol, it can also exert a bactericidal effect at the dose of 30 mg/kg administerred intramuscularly in the case of septicaemia, while in arthritis it can only have a bacteriostatic effect against strains of S. suis below the MIC value 2 µg/ml.



List of lectures