Pharmacokinetics, urinary excretion and milk penetration of difloxacin in healthy and experimentally E. coli infected lactating goats

The pharmacokinetics of difloxacin was studied following single intravenous and intramuscular injection at a dose of 5 mg/kg b.wt. and following repeated intramuscular injections in healthy and experimentally infected goats. The pharmacokinetic parameters following a single intravenous injection of 5 mg difloxacin/kg b.wt. in healthy goats revealed that the drug obeyed a two compartments open model with distribution half-life [t0.5(α)] equal to 0.22 h, elimination half-life [t0.5(β)] equal to 5.65 h. The volume of distribution (Vdss) was 0.735 L/kg and total clearance of the drug (CLtot=0.10 L/kg/h). Following a single intramuscular injection of 5 mg difloxacin/ kg. b.wt., the drug reached its maximum serum concentrations after 2 hours of injection (3.92 μg/ml). Difloxacin could be detected in serum in a therapeutic level for 24 h with absorption half life [t0.5(ab)] was (0.46 h), the elimination half life [t0.5(el)] was (5.64 h). The mean systemic bioavailability of difloxacin following intramuscular injection in healthy goats was 86.46%. The extent of serum protein binding of difloxacin in goats was 12.05%. The serum concentrations of difloxacin following repeated intramuscular injections of 5 mg/kg.b.wt. once daily for 5 consecutive days, peaked 2 h after each intramuscular dose with lower significant values recorded in experimentally infected goats than in normal ones. Urine and milk concentrations of difloxacin were decreased significantly in infected than in healthy goats following repeated intramuscular injections. Following intramuscular injection of 5 mg/kg.b. wt of difloxacin for 5 consecutive days, difloxacin showed a cumulative behaviour in serum, urine and milk of goats. Results of this study indicated that difloxacin was useful for treatment of urinary tract infections and mastitis in goats.