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Further information
Advocin 180 is rapidly and extensively absorbed from the site of injection. Bioavailability is around 90%. Danofloxacin is only poorly metabolised and subsequently eliminated via both the renal and hepatic routes. A difference in elimination kinetics is observed between pre-ruminant animals (half-life of 12 hours) and ruminant animals (half-life of 4 hours). Following a single subcutaneous administration at 6 mg/kg body weight, peak plasma and tissue concentrations are achieved within one to two hours after treatment. High drug concentrations in lung, enteric and lymphatic tissues are observed with concentrations in lung and enteric tissues approximately four times greater than in plasma. The dose selected for Advocin 180 was based on the optimisation of the concentration dependent bactericidal activity of danofloxacin against respiratory and enteric pathogens.
The mean milk concentrations of danofloxacin were 4.61 and 0.2 µg/ml at the 8 and 24 hour milking, respectively, following a single subcutaneous injection.
Heavy reliance on a single class of antibiotic may result in the induction of resistance in a bacterial population. Cross-resistance to fluoroquinolones can occur.
The antimicrobial activity of danofloxacin is based upon the inhibition of microbial DNA gyrase and topoisomerase IV. The inhibitory effect is on the second step of the enzymatic process, uncoupling the breakage and reunion functions. Danofloxacin produces a stable complex between the enzyme and DNA. This results in the cessation of DNA replication and transcription. The bactericidal effect is also observed on bacteria in the stationary growth phase. Although there is the possibility for cross resistance developing within any class of antimicrobial, because of the specific mode of action of fluoroquinolones cross resistance with other major antibiotics which act on the cell wall or on protein synthesis is unlikely to occur. Danofloxacin is efficacious in the treatment of field cases of acute mastitis with a Gram negative bacterial aetiology.