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Pharmacological particulars
Pharmacotherapeutic group: Antibacterials for systemic use, Amphenicols. ATCvet code: QJ01BA90
Pharmacodynamic properties
Florfenicol is a synthetic broad-spectrum antibiotic effective against most Gram positive and Gram negative bacteria isolated from domestic animals.
Florfenicol acts by inhibiting bacteria protein synthesis at the ribosomal level, thus is bacteriostatic. However, in vitro tests have shown that florfenicol has a bactericidal activity against the most commonly isolated bacterial pathogens involved in respiratory diseases:
- Histophilus somni, Mannheimia haemolytica and Pasteurella multocida isolated from cattle
- Actinobacillus pleuropneumonia, and Pasteurella multocida isolated from pigs.
Acquired resistance to florfenicol is mediated by efflux pump resistance associated with a floR gene. Such resistance has not yet been identified in the target pathogens except for Pasteurella multocida. Cross resistance with chloramphenicol can occur. Resistance to florfenicol and other antimicrobials has been identified in the food-born pathogen Salmonella typhimurium and co-resistance with the third-generation cephalosporins has been observed in respiratory and digestive Escherichia coli.
For Mannheimia haemolytica, Pasteurella multocida and Histophilus somni the following breakpoints have been determined for florfenicol in bovine respiratory disease; susceptible: ≤2 µg/ml, intermediate: 4 µg/ml, resistant: ≥8 µg/ml.
In bovine, 99% of P. multocida isolates (n=156) and 98% of M. haemolytica isolates (n=109) were susceptible to florfenicol (strains isolated in France in 2012).
In swine, 99% of P. multocida isolates (n=150) were susceptible to florfenicol (strains isolated in France in 2012).
The following Minimum Inhibitory Concentrations (MIC) have been determined for florfenicol in European isolates collected from diseased animals between 2009 to 2012:
Bacteria species
Origin
Nb of strains
CMI of florfenicol (µg/mL)
CMI50
CMI90
Mannheimia haemolytica
Cattle
147
0.7
1.0
Pasteurella multocida
Cattle
134
0.3
0.5
Histophilus somni
Cattle
64
0.2
0.2
Pasteurella multocida
Swine
151
0.4
0.5
Actinobacillus pleuropneumoniae
Swine
158
0.2
0.4
Pharmacokinetic particulars
In cattle:
Intramuscular administration of the formulation at the recommended dose of 20 mg/kg maintains efficacious blood levels for 48 hours. Maximum mean serum concentration (Cmax) of 3.8 µg/ml occurred 5.7 hours (Tmax) after dosing. The mean serum concentration 24 hours after dosing was 1.95 µg/ml. The mean elimination half life was 15.3 hours
In pigs:
After intramuscular administration of florfenicol, maximum serum concentration of 4.7 µg/ml is reached after 1.8 hours and the concentrations deplete with a terminal mean half-life of 14.8 hours. Serum concentrations drop below 1 µg/ml, the MIC90 for the target porcine pathogens, 12-24 hours following IM administration. Florfenicol concentrations achieved in lung tissue reflect plasma concentration, with a lung: plasma concentration ratio of approximately 1. After administration to pigs by the intramuscular route, florfenicol is rapidly excreted, primarily in urine. The florfenicol is extensively metabolised.