ATCvet code: QJ01BA99
Pharmacotherapeutic Group
Antibacterials for systemic use, amphenicols, combinations.
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 bacterial protein synthesis at the ribosomal level and is bacteriostatic. Laboratory tests have shown that florfenicol is active against the most commonly isolated bacterial pathogens involved in bovine respiratory disease which include M. bovis, M. haemolytica, P. multocida and H. somni. Florfenicol is considered to be a bacteriostatic agent, but in vitro studies of florfenicol demonstrate bactericidal activity against M. haemolytica, P. multocida and H. somni. Florfenicol bactericidal activity was characterised as essentially time dependant against the three target pathogens with the possible exception of H. somni where a concentration dependency was observed. During the florfenicol susceptibility monitoring program (2000-2003) a total of 487 M. haemolytica, 522 P. multocida and 25 H. somni isolates were collected. MIC values ranged between <0.12 and 2 µg/ml for M. haemolytica (MIC90 = 1 µg/ml), between <0.12 and 2 µg/ml for P. multocida (MIC90 = 0.50 µg/ml) and between 0.12 and 0.5 µg/ml for H. somni. Breakpoints have been established by the CLSI (Clinical and Laboratory Standard Institute) for bovine respiratory pathogens as follows (see table):
Table for Resflor 300/16.5 mg/ml |
| | | | | | | |
Pathogen | Florfenicol Disk Concentration (µg) | Diameter (mm) | MIC (µg/ml) |
| | S | I | R | S | I | R |
M. haemolytica P. multocida H. somni | 30 | ≥19 | 15-18 | ≤14 | ≤2 | 4 | ≥8 |
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There are no established breakpoints for M. bovis nor have culture techniques been standardized by CLSI. Despite a reduction in M. bovis pathogen load, M. bovis may not be fully eliminated from the lungs after treatment with the veterinary medicinal product.
The only mechanisms of chloramphenicol resistance that are known to have significant clinical relevance are CAT-mediated inactivation and efflux-pump resistance. Of these, only some of the efflux mediated resistance would also confer resistance to florfenicol and thus have the potential to be affected by florfenicol use in animals. Resistance to florfenicol in the target pathogens has only been reported on rare occasions and was associated with efflux pump and the presence of the floR gene. Flunixin meglumine is a non-steroidal anti-inflammatory drug with analgesic and antipyretic activity. Flunixin meglumine acts as a reversible non-selective inhibitor of cyclo-oxygenase (both COX 1 and COX 2 forms), an important enzyme in the arachidonic acid cascade pathway which is responsible for converting arachidonic acid to cyclic endoperoxides. Consequently, synthesis of eicosanoids, important mediators of the inflammatory process involved in central pyresis, pain perception and tissue inflammation, is inhibited. Through its effects on the arachidonic acid cascade, flunixin also inhibits the production of thromboxane, a potent platelet pro-aggregator and vasoconstrictor which is released during blood clotting. Flunixin exerts its antipyretic effect by inhibiting prostaglandin E2 synthesis in the hypothalamus. Although flunixin has no direct effect on endotoxins after they have been produced, it reduces prostaglandin production and hence reduces the many effects of the prostaglandin cascade. Prostaglandins are part of the complex processes involved in the development of endotoxic shock.
Pharmacokinetic properties
The administration of the product by the subcutaneous route at the recommended dosage of 40 mg/kg florfenicol maintained efficacious plasma levels in cattle above a MIC90 of 1 µg/ml for approximately 50 hours and above a MIC90 of 2 µg/ml for approximately 36 hours. Maximum plasma concentration (Cmax) of approximately 9.9 µg/ml occurred approximately 8 hours (Tmax) after dosing.
After administration of the product by the subcutaneous route at the recommended dosage of 2.2 mg/kg flunixin peak plasma concentrations of 2.8 µg/ml were achieved after 1 hour.
The binding of florfenicol on proteins is approximately 20% and for flunixin > 99%. The degree of elimination of florfenicol residues in urine is approximately 68% and in faeces approximately 8%. The degree of elimination of flunixin residues in urine is approximately 34% and for faeces approximately 57%.
Environmental properties
Flunixin is toxic to avian scavengers although foreseen low exposure leads to low risk.