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

Abstract

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 (fAUC/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.