ATCvet code: QJ01MA97

The primary mode of action of the fluoroquinolones involves interaction with enzymes essential for major DNA functions such as replication, transcription and recombination. The primary targets for pradofloxacin are the bacterial DNA gyrase and topoisomerase IV enzymes. Reversible association between pradofloxacin and DNA gyrase or DNA topoisomerase IV in the target bacteria results in inhibition of these enzymes and rapid death of the bacterial cell. The rapidity and extent of bacterial killing are directly proportional to the drug concentration.

Although pradofloxacin has in-vitro activity against a wide range of Gram-positive and Gram­negative organisms, including anaerobic bacteria, this veterinary medicinal product should only be used for the approved indications and in accordance with the prudent use recommendations in section 'special precautions for use'.

The bacteria were isolated between 2001 and 2007 from clinical cases in Belgium, France, Germany, Hungary, Poland, Sweden and UK.

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.

In laboratory studies the bioavailability of pradofloxacin was reduced in fed dogs and cats compared to fasted animals. However in the clinical studies feeding did not reveal any impact on the treatment effect.

After oral administration of the therapeutic dose to dogs, pradofloxacin is rapidly (T max of 2 hours) and almost completely (approximately 100%) absorbed reaching peak concentrations of 1.6 mg/1.

A linear relationship between pradofloxacin serum concentrations and the administered dose is observed in dogs within a tested dose range of 1 to 9 mg/kg body weight. Long-term daily treatment has no impact on the pharmacokinetic profile, with an accumulation index of 1.1. In vitro plasma protein binding is low (35%). The high volume of distribution (V d) >21/kg bodyweight indicates good tissue penetration. Pradofloxacin concentrations in skin homogenates of dogs exceed those in serum by up to seven times.

Pradofloxacin is eliminated from serum with a terminal half-life of7 hours. Major elimination pathways are glucuronidation as well as renal excretion. Pradofloxacin is cleared from the body at 0.241/h/kg. Approximately 40% of the administered product is excreted unchanged via the kidneys.

In cats, absorption of orally administered pradofloxacin at the therapeutic dose is rapid reaching peak concentrations of 1.2 mg/1 within 0.5 hours. The bioavailability of the tablet is at least 70%. Repeated dosing shows no impact on the pharmacokinetic profile (accumulation index = 1.0). In vitro plasma protein binding is low (30%). The high volume of distribution (V d) >41/kg body weight indicates good tissue penetration.

Pradofloxacin is eliminated from serum with a terminal half-life of9 hours. The major elimination pathway in cats is glucuronidation. Pradofloxacin is cleared from the body at 0.28 1/h/kg.