Integration of Pharmacokinetic and Pharmacodynamic Indices of Orbifloxacin in Beagle Dogs after a Single Intravenous and Intramuscular Administration

Abstract

ABSTRACT The pharmacokinetics (PK) and pharmacodynamics (PD) of orbifloxacin were studied in beagle dogs after intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 2.5 mg/kg body weight. An absolute bioavailability of 100.1% ± 4.76%, a terminal half-life of 4.23 ± 0.2 h and 3.95 ± 0.15 h after i.v. and i.m. administration, a steady-state volume of distribution of 1.61 ± 0.13 liters/kg, and clearance of 0.31 ± 0.03 liters/h/kg were observed. Orbifloxacin showed rapid, concentration-dependent killing against the Escherichia coli , Staphylococcus aureus , Staphylococcus intermedius , and Proteus mirabilis clinical isolates. Computations based on PK-PD analysis indicated that the recommended dose is unlikely to be clinically effective against some strains like S. intermedius . Therefore, a higher dose of orbifloxacin would be worthy of consideration for treatment of certain bacterial infections in dogs.