Pharmacokinetics of difloxacin in healthy and E. coli-infected broiler chickens

Abstract

1. The pharmacokinetics of difloxacin were investigated in healthy and E. coli-infected broiler chickens following intravenous and oral administration of a single dose of 10 mg/kg bodyweight.

2. After intravenous injection of difloxacin, the serum concentration–time curves were best described by a two-compartment open model. The distribution and elimination half-lives (t_0.5α) and (t_0.5el), respectively, were 0.10 ± 0.016 h and 3.7 ± 0.08 h in healthy chickens compared with 0.05 ± 0.005 h and 6.42 ± 0.71 h in E. coli-infected birds. The volumes of distribution V_dss were 3.14 ± 0.11 and 9.25 ± 0.43 l/kg, with total body clearance (Cl_tot) of 0.65 ± 0.018 and 1.14 ± 0.1 ml/kg/h, respectively.

3. Following oral administration, difloxacin was absorbed with t_0.5(ab) of 0.57 ± 0.06 and 0.77 ± 0.04 h and was eliminated with t_0.5(el) of 4.7 ± 0.34 and 3.42 ± 0.19, respectively, in normal and infected chickens. The peak serum concentrations were 1.34 ± 0.09 and 1.05 ± 0.06 µg/ml and attained a T_max of 2.27 ± 0.07 and 2.43 ± 0.06 h, respectively. The systemic bioavailability of difloxacin following oral administration was 86.2% in healthy chickens and 90.6% in E. coli-infected birds. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of difloxacin against the field strain of E. coli O78 in vitro were 0.02 µg and 0.04 µg/ml, respectively.

4. These results show that administration of a therapeutic dose of difloxacin is effective in the treatment of E. coli infection in chickens. The serum concentration of the drug was much higher than the MIC of the E. coli O78 strain in both healthy and infected chickens.