ATCvet code: QJ01MA90
Pharmacodynamic properties
Mode of action
Enrofloxacin belongs to the fluoroquinolone group of antibiotics. Two enzymes essential in DNA replication and transcription, DNA gyrase and topoisomerase IV, have been identified as the molecular targets of fluoroquinolones. Target inhibition is caused by non-covalent binding of fluoroquinolone molecules to these enzymes. Replication forks and translational complexes cannot proceed beyond such enzyme-DNA-fluoroquinolone complexes, and inhibition of DNA and mRNA synthesis triggers events resulting in a rapid, drug concentration-dependent killing of pathogenic bacteria. The mode of action of enrofloxacin is bactericidal and bactericidal activity is concentration dependent.
Antibacterial spectrum
Enrofloxacin is active against Gram-positive and many Gram-negative bacteria such as Histophilus somni, Mannheimia haemolytica, Pasteurella multocida, Mycoplasma spp. and E. coli in cattle as well as Actinobacillus pleuropneumoniae, Pasteurella multocida and Haemophilus parasuis in pigs at the recommended therapeutic doses.
Types and mechanisms of resistance
Resistance to fluoroquinolones has been reported to arise from five sources, (i) point mutations in the genes encoding for DNA gyrase and/or topoisomerase IV leading to alterations of the respective enzyme, (ii) alterations of drug permeability in Gram-negative bacteria, (iii) efflux mechanisms, (iv) plasmid mediated resistance and (v) gyrase protecting proteins. All mechanisms lead to a reduced susceptibility of the bacteria to fluoroquinolones. Cross-resistance within the fluoroquinolone class of antimicrobials is common.
Clinical breakpoints established by CLSI1 in 2024 for enrofloxacin cattle for bovine respiratory disease are as follows:
Organism | Minimum inhibitory concentration breakpoints of enrofloxacin (μg/ml) |
susceptible | intermediate | resistant |
Histophilus somni | ≤0.25 | 0.5-1 | ≥2 |
Mannheimia haemolytica | ≤0.25 | 0.5-1 | ≥2 |
Pasteurella multocida | ≤0.25 | 0.5-1 | ≥2 |
Clinical breakpoints established by CLSI1 in 2024 for enrofloxacin in pigs for porcine respiratory disease are as follows:
Organism | Minimum inhibitory concentration breakpoints of enrofloxacin (μg/ml) |
susceptible | intermediate | resistant |
Actinobacillus pleuropneumoniae | ≤0.25 | 0.5 | ≥1 |
Pasteurella multocida | ≤0.25 | 0.5 | ≥1 |
CLSI. Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals: 7th ed. CLSI supplement Vet01S Clinical and Laboratory Standards Institute.
Pharmacokinetic particulars
Following subcutaneous administration of the veterinary medicinal product in cattle or intramuscular administration in pigs, the active substance, enrofloxacin, is absorbed very rapidly and almost completely (high bioavailability).
Cattle:
After subcutaneous administration at a dose rate of 7.5 mg enrofloxacin per kg body weight to non-lactating cattle peak plasma concentrations of 0.82 mg/L are reached within 5 hours. The overall drug exposure in plasma is 9.1 mg*hr/L. Enrofloxacin is eliminated from the body at a half-life of 6.4 hr. Approximately 50% of enrofloxacin is metabolised to the active substance ciprofloxacin. Ciprofloxacin is eliminated from the body at a half-life of 6.8 hr.
After intravenous injection at a dose rate of 5.0 mg enrofloxacin per kg body weight to lactating cows, peak plasma concentrations of approx. 23 mg/L are reached immediately. The overall drug exposure in plasma is 4.4 mg*hr/L. Enrofloxacin is eliminated from the body at a half-life of 0.9 hr. Approximately 50% of parent compound is metabolised to ciprofloxacin with peak plasma concentrations of 1.2 mg/L reached at 0.2 hr. Mean elimination half-life of ciprofloxacin is 2.1 hr.
In milk the metabolite ciprofloxacin mainly accounts for antibacterial activity (approx. 90%). Ciprofloxacin reaches peak milk concentrations of 4 mg/L within 2 hr after intravenous dosing. Total exposure in milk over 24 hours is approx. 21 mg*hr/L. Ciprofloxacin is eliminated from milk at a half-life of 2.4 hr. Peak concentrations of 1.2 mg enrofloxacin per litre are reached in milk within 0.5 hours with an total enrofloxacin exposure in milk of approx. 2.2 mg*hr/L. Enrofloxacin is eliminated from milk at 0.9 hr.
Pigs:
After intramuscular administration of 7.5 mg/kg body weight to pigs a mean peak serum concentration of 1.46 mg/L was achieved within 4 hours. The overall drug exposure over 24 hours was 20.9 mg*hr/L. The drug was eliminated from the central compartment at a terminal half-life of 13.1 hr. With peak concentrations less than 0.06 mg/L mean serum concentrations of ciprofloxacin were very low.
Enrofloxacin has a high volume of distribution. The concentrations in the tissues and organs mostly significantly exceed serum levels. Organs in which high concentrations can be expected include the lungs, liver, kidneys, gut and muscle tissue.
Enrofloxacin is eliminated renally.