Pharmacokinetics of difloxacin in pigs and broilers following intravenous, intramuscular, and oral single-dose applications

Abstract

Pharmacokinetics of difloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of five (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analyzed by a compartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half-lives (t1/2β) were 17.14 ± 4.14, 25.79 ± 8.10, 16.67 ± 4.04 (pigs) and 6.11 ± 1.50, 5.64 ± 0.74, 8.20 ± 3.12 h (broilers), respectively. After single i.m. and p.o. administration, difloxacin was rapidly absorbed, with peak plasma concentrations (Cmax) of 1.77 ± 0.66, 2.29 ± 0.85 (pigs) and 2.51 ± 0.36, 1.00 ± 0.21 μg/mL (broilers) attained at t max of 1.29 ± 0.26, 1.41 ± 0.88 (pigs) and 0.86 ± 0.4, 4.34 ± 2.40 h (broilers), respectively. Bioavailabilities (F) were (95.3 ± 28.9)% and (105.7 ± 37.1)% (pigs) and (77.0 ± 11.8)% and (54.2 ± 12.6)% (broilers) after i.m. and p.o. doses, respectively. Apparent distribution volumes(Vd(area)) of 4.91 ± 1.88 and 3.10 ± 0.67 L/kg and total body clearances(Cl B) of 0.20 ± 0.06 and 0.37 ± 0.10 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), the half-lives of both absorption and distribution(t1/2ka, t 1/2α) were also determined. Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 5 mg/kg given intramuscularly every 24 h in pigs, or administered orally every 24 h at the dosage of 10 mg/kg in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC90 are <0.25 μg/mL and <0.1 μg/mL respectively. © 2008 The Authors.