Disposition of ofloxacin in female New Zealand White rabbits

Limited information exists regarding the disposition of ofloxacin in rabbits. Pharmacokinetic information is necessary for the design of appropriate therapeutic regimens for the treatment of organisms (e.g. Pasteurella multocida) commonly infecting this species. This study evaluated the pharmacokinetics of ofloxacin following intravenous (i.v.) and subcutaneous (s.c.) administration. Two groups of three female New Zealand White rabbits received a single dose of 20 or 40 mg/kg by the i.v. and s.c. routes. Samples were collected prior to drug administration, then 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 h postdose. Ofloxacin concentrations in serum were determined using a validated HPLC assay. Mean maximum concentrations were 66.86 +/- 10.83 mg/L and 14.1 +/- 2.20 mg/L for the i.v. and s.c. administration of 20 mg/kg. The 40 mg/kg dose produced maximum concentrations of 154.96 +/- 35.45 mg/L and 23.83 +/- 4.01 mg/L for the i.v. and s.c. doses, respectively. The area under concentration-time curve increased proportionally with the dose, while the half-life was unaltered and ranged from 1.5-1.9 h. From these data, it appears that a 20 mg/kg dose administered every 8 h by the s.c. route would optimize the pharmacodynamic profile of ofloxacin and provide an appropriate regimen for the treatment of many susceptible organisms which commonly infect this species.