Marbofloxacin is a new fluoroquinolone developed exclusively for veterinary use. Minimum inhibitory concentrations of marbofloxacin were assessed for 816 recent isolates associated with canine or feline diseases. Marbofloxacin showed a broad spectrum of activity against gram-negative and gram-positive bacteria. In vitro rates of killing of marbofloxacin and enrofloxacin were compared against strains of Staphylococcus intermedius and Pasteurella multocida, and the results showed no marked difference between the two antibiotics. The duration of bactericidal activity was evaluated ex vivo in the urine of dogs and cats treated with marbofloxacin and lasted from 2 to 5 days after a single administration according to the dosages. Post-antibiotic effect durations were determined with Escherichia coli, Pasteurella multocida, Staphylococcus aureus and Staphylococcus intermedius and were found almost equal to those of enrofloxacin or ciprofloxacin. These results predict a great potential for marbofloxacin in the treatment of a wide range of diseases in dogs and cats.

Six dogs were treated with a single intravenous (i.v.) dose (2 mg/kg) of marbofloxacin, followed by single oral (p.o.) doses of marbofloxacin at 1, 2 and 4 mg/kg, according to a three-way crossover design. The same experimental design was used for the subcutaneous (s.c.) route. In addition, a long-term trial involving eight dogs given oral doses of marbofloxacin at 2, 4 and 6 mg/kg/day for thirteen weeks was carried out. Plasma and urine samples were collected during the first two trials, plasma and skin samples were collected after the second of these trials. Plasma, urine and skin concentrations of marbofloxacin were determined by a reverse phase liquid chromatographic method. Mean pharmacokinetic parameters after i.v. administration were the following: t1/2 beta = 12.4 h; ClB = 0.10 L/h.kg; Varea = 1.9 L/kg. The oral bioavailability of marbofloxacin was close to 100% for the three doses. At 2 mg/kg, Cmax of 1.4 micrograms/mliter was reached at tmax of 2.5 h. Mean AUC and Cmax values had a statistically significant linear relationship with the doses administered. About 40% of the administered dose was excreted in urine as unchanged parent drug. After s.c. administration, the calculated parameters were close to those obtained after oral administration, except tmax (about 1 h) which was shorter. The mean skin to plasma concentration ratio after the long-term trial was 1.6, suggesting good tissue penetration of marbofloxacin.

The efficacy and tolerability of a marbofloxacin-clotrimazole-dexamethasone otic suspension (MCD) was compared with a standard topical treatment using a phase III clinical trial protocol. In a total of 140 dogs with clinical signs of acute or subacute otitis externa, Staphylococcus, Pseudomonas, Enterobacteriaceae and Malassezia were isolated from samples taken at inclusion to identify the causative pathogen; a further sample was collected in the event of failure or relapse, and from dogs (at day 14) for which Pseudomonas species had been isolated at inclusion. One group received MCD (10 drops per affected ear) once daily and a second received Surolan (containing polymyxin B, miconazole and prednisolone) (5 drops per affected ear), twice daily. Each group received treatment for 7 or 14 days according to the clinical outcome on day 7. Efficacy and tolerability were evaluated on days 7, 14 and, if necessary, 28 for dogs treated for 14 days. The trial demonstrated equivalence of both treatments in terms of efficacy, with a cure rate of 58.3% for MCD and 41.2% for Surolan. Both medications were equally well tolerated by dogs, but MCD was superior in terms of pain relief, decrease in pus quantity and smell, response rate and investigator's assessment on day 14.

The plasma and milk pharmacokinetics of marbofloxacin, a fluoroquinolone antibacterial compound, were evaluated in dairy cows, as well as its pharmacodynamic characteristics against mastitis-isolated pathogens. Marbofloxacin was given intramuscularly as a 10% aqueous solution to dairy cows either at a single dose or at repeated doses of 2 mg/kg once daily for 3 d. Blood and milk samples were collected for the determination of the concentration of marbofloxacin and of its putative metabolites: N-desmethyl-marbofloxacin and N-oxide-marbofloxacin. Bacterial field isolates were from milk samples collected from dairy cows suspected of having an intramammary infection. After identification, the minimal inhibitory concentration (MIC) was determined against the isolated strains. The maximal marbofloxacin concentration (Cmax) observed in milk after the first administration was 1.024 microg/mL, and the area under the curve during the first dosing interval was 6.513 microg/h per milliliter. After the third administration, these parameters were slightly increased (about 20% at most). Both metabolites were detected in the milk, but their concentrations were below the limit of quantification. The MIC against 90% of the population (MIC90) of Escherichia coli was 0.016 microg/mL, and it was 0.229 microg/mL against Staphylococcus aureus. The following surrogate clinical outcome markers were obtained against E. coli strains: a Cmax/MIC ratio of 67 and an area under the curve/MIC ratio of 407 h. Hence, a possible efficacy of marbofloxacin in the treatment of E. coli-induced mastitis could be expected as the endpoints of 10 and 250 h, respectively, are reached.

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