ATCvet code: QJ01MA90.
Pharmacodynamics
Enrofloxacin is a synthetic, broad spectrum antimicrobial substance, belonging to the fluoroquinolone group of antibiotics.
Mode of action:
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 many Gram-negative bacteria such as Escherichia coli, Klebsiella spp., Actinobacillus pleuropneumoniae, Mannheimia haemolytica, Pasteurella spp. (e.g. Pasteurella multocida), against Gram-positive bacteria such as Staphylococcus spp. (e.g. Staphylococcus aureus) and against Mycoplasma spp. 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.
MIC clinical breakpoints
Cattle:
Clinical breakpoints established by CLSI1 in 2024 for enrofloxacin in cattle for bovine respiratory disease are as follows:
Organism | Minimum inhibitory concentration breakpoints of enrofloxacin (μg/ml) |
susceptible | intermediate | resistant |
Mannheimia haemolytica | <0.25 | 0.5-1 | >2 |
Pasteurella multocida | <0.25 | 0.5-1 | >2 |
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
Pig:
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 | >1 |
Pasteurella multocida | <0.25 | 0.5-1 | >1 |
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 InstitutePharmacokinetics
Enrofloxacin is rapidly absorbed after parenteral injection. Bioavailability is high (approximately 100% in pig and cattle) with a low to moderate plasma protein binding (approximately 20 to 50%). Enrofloxacin is metabolized to the active substance ciprofloxacin at approximately 40% in ruminants and less than 10% in pigs.
Enrofloxacin and ciprofloxacin distribute well into all target tissues, e.g. lung, kidney, skin and liver, reaching 2- to 3-fold higher concentrations than in plasma. Parent substance and active metabolite are cleared from the body via urine and faeces.
Accumulation in plasma does not occur following a treatment interval of 24 h.
In milk, most of drug activity consists on ciprofloxacin. Overall drug concentrations peak at 2 hours after treatment showing an approximately 3-fold higher total exposure over the 24 hours dosing interval compared to plasma.
| Pigs | Pigs | Cattle | Cattle |
Dose rate (mg/kg bw) | 2.5 | 5 | 5 | 5 |
Route of administration | im | im | iv | sc |
Tmax (h) | 2 | 2 | / | 3.5 |
Cmax (mcg/ml) | 0.7 | 1.6 | / | 0.733 |
AUC (mcg∙h/ml) | 6.6 | 15.9 | 9.8 | 5.9 |
Terminal half-life (h) | 13.12 | 8.10 | / | 7.8 |
Elimination half-life (h) | 7.73 | 7.73 | 2.3 | |
F (%) | 95.6 | / | / | 88.2 |