Pradofloxacin pharmacokinetics after oral and intravenous administration in dogs reveal plasma concentrations sufficient to treat infections caused by susceptible bacteria

Objective To determine the pharmacokinetics of pradofloxacin following oral and IV administration of a concentrated solution available in the US and whether the plasma pradofloxacin concentration would be sufficient to treat susceptible bacterial infections. Methods Pradofloxacin was administered orally and IV as a 200-mg/mL solution at a dose of 10 mg/kg to 6 healthy dogs in a crossover study design, with treatments separated by a minimum 2-day washout period. Blood samples were collected for the measurement of plasma pradofloxacin concentration via HPLC. Pharmacokinetic analysis was performed with nonlinear mixed-effects modeling. Results After oral administration of pradofloxacin, the peak plasma concentration was 3.4 μg/mL, and the elimination half-life was 5.42 hours, with oral bioavailability of 69%. After IV administration, the elimination half-life was 8.1 hours, systemic clearance was 0.20 L/kg/h, and volume of distribution was 2.06 L/kg. Conclusions There were no adverse effects from direct IV injection of pradofloxacin, and the drug was well absorbed when administered orally as the solution. Clinical Relevance The concentrations from each route were sufficient to reach the free drug concentration area-under-the-curve/MIC ratio ( f AUC/MIC) pharmacokinetic-pharmacodynamic targets for treating infections caused by gram-positive and gram-negative bacteria in the susceptible category of ≤ 0.25 μg/mL according to clinical breakpoints approved by the Clinical and Laboratory Standards Institute.