Pharmacotherapeutic group: Antibacterials for systemic use, fluoroquinolones.
ATCvet code: QJ01MA90.
Pharmacodynamic properties
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, Pasteurella spp. (e.g. Pasteurella multocida), Bordetella spp., Proteus spp., Pseudomonas spp., 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.
Pharmacokinetic particulars
Enrofloxacin is rapidly absorbed after parenteral injection. Bioavailability is high (approximately 100% in pigs) with a low to moderate plasma protein binding (approximately from 20 to 50%). Enrofloxacin is metabolized to the active substance ciprofloxacin at approximately 40% in dogs and less than 10% in cats and pigs.
African Grey Parrots serum ciprofloxacin concentrations were 3–78% of the enrofloxacin dose, with an increasing ciprofloxacin/enrofloxacin ratio with multiple doses.
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.
| Dogs | Cats | Rabbits | Pigs | Pigs |
Dose rate (mg/kg bw) | 5 | 5 | 10 | 2.5 | 5 |
Route of administration | sc | sc | sc | im | im |
Tmax (h) | 0.5 | 2 | / | 2 | 2 |
Cmax (µg/ml) | 1.8 | 1.3 | / | 0.7 | 1.6 |
AUC (µg∙h/ml) | / | / | / | 6.6 | 15.9 |
Terminal half-life (h) | / | / | / | 13.12 | 8.10 |
Elimination half-life (h) | 4.4 | 6.7 | 2.5 | 7.73 | 7.73 |
F (%) | / | / | / | 96.6 | / |