Pharmacotherapeutic group: Fluoroquinolone.
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 floroquinolones. They modulate the topological state of DNA through cleaving and resealing reactions. Initially, both strands of the DNA double helix are cleaved. Then, a distant segment of DNA is passed through this brek before the strands are resealed. Target inhibition is caused by non-covalent binding of fluroquinolone molecules to an intermediate state in this sequence of reactions, in which DNA is cleaved, but both strands are retained covalently attached to the enzymes. Replication forks and translational complexes cannot proceed beyond such enzyme-DNA-fluroquinolone, and inhibition of DNA and mRNA synthesis triggers events resulting in a rapid, drug concentration-dependent killing of pathogenic bacteria.
Antibacterial spectrum
Enrofloxacin is active against many Gram-negative bacteria, against Gram-positive bacteria and Mycoplasma spp
In vitro susceptibility has been shown in strains of (i) Gram-negative species such as Escherichia coli, Pasteurella multocida and Avibacterium (Haemophilus) paragallinarum and (ii) Mycoplasma gallisepticum and Mycoplasma synoviae.
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 susceptiblity of the bacteria to fluoroquinolones. Cross-resistance within the fluoroquinolone class of antimicrobials is common.
Pharmacokinetic particulars
The pharmacokinetics of enrofloxacin are such that oral and parenteral administration leads to similar serum levels. Enrofloxacin possesses a high distribution volume. Tissue levels 2-3 times higher than that found in the serum, have been demonstrated in laboratory animals and target species. Organs in which high levels can be expected are the lungs, liver, kidney, skin, bone and lymphatic system. Enrofloxacin also distributes into the cerebrospinal fluid and the aqueous humour.
The degree of metabolism depends on the species and ranges between 50-60%. Biotransformation at hepatic level of enrofloxacin results in the active metabolite, ciprofloxacin. In general, metabolism is by hydroxylation and oxidation processes.
Excretion occurs by biliary and renal route, with excretion in the urine predominating.