Ex vivo antibacterial activity of levofloxacin against Escherichia coli and its pharmacokinetic profile following intravenous and oral administrations in broilers

The use of antibiotics is common for prevention and treatment of diseases. However, determination of optimal dosage in the target animal is necessary for success of a treatment. This study aimed to evaluate the pharmacokinetics/pharmacodynamics (PK/PD) of levofloxacin, a third generation fluoroquinolone, in broilers. Parallel study design was used and each group of animals (n=20) received levofloxacin intravenously (IV) and orally (PO) at a dose of 5 mg/kg. Plasma and serum and tissues were collected for PK and PD studies. Plasma concentrations of levofloxacin were determined by HPLC with fluorescence detector. As a PD study, minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined against E. coli which was isolated in clinical broilers. Ex vivo antibacterial activity of levofloxacin against E. coli was evaluated using the time killing method. Mean values of terminal half-life for IV and PO groups were 6.93 and 8.09 h, respectively. Following oral administration, the peak plasma concentration was achieved at 0.88 h (Tmax). Mean value of oral bioavailability was 123.25%. Levofloxacin residues were found in all the tissues tested (muscle, liver, kidney and lung). The highest concentration was found in the liver. Plasma concentration above 8 x MIC lead to eradication of E. coli over an incubation period of 24h. The results of ex vivo growth inhibition curves were consistent with the in vitro time-kill study. Levofloxacin showed plasma concentration dependent antibacterial activity against a clinical isolate of E. coli. According to the assessment of PK/PD relationship, administration of levofloxacin at a dose of 5 mg/kg seems to be effective in killing E. coli. Also, simulated optimal dose based on the ex vivo PK/PD approach was up 2.9 mg/kg/day (bactericidal) to 4.3 mg/kg/day (eradication) PO against E. coli (MIC = 0.125 µg/ml).