Comparative study of the plasma pharmacokinetics and tissue concentrationsof danofloxacin and enrofloxacin in broiler chickens

The plasma pharmacokinetics of danofloxacin and enrofloxacin in broiler chi ckens was investigated following single intravenous (i.v.) or oral administ ration (p.o.), and the steady-state plasma and tissue concentrations of bot h drugs were investigated after continuous administration via the drinking water. The following dosages approved for the treatment of chickens were us ed: danofloxacin 5 mg/kg and enrofloxacin 10 mg/kg of body weight. Concentr ations of danofloxacin and enrofloxacin including its:metabolite ciprofloxa cin were determined in plasma and eight tissues by specific and sensitive h igh performance liquid chromatography methods. Pharmacokinetic parameter va lues for both application routes calculated by noncompartmental methods wer e similar for danofloxacin compared to enrofloxacin with respect to elimina tion half-life (t(1/2); approximate to 6-7 h), mean residence time (MRT; 6- 9 h) and mean absorption time (MAT; 1.44 vs. 1.20 h). However, values were twofold higher for body clearance (Cl-B; 24 vs. 10 mL/min. kg) and volume o f distribution at steady state (Vd(SS); 10 vs. 4 L/kg). Maximum plasma conc entration (C-max) after oral administration was 0.5 and 1.9 mu g/mL. for da nofloxacin and enrofloxacin, respectively, occurring at 1.5 h for both drug s. Bioavailability (F) was high: 99% for danofloxacin and 89% for enrofloxa cin. Steady-state plasma concentrations (mean +/- SD) following administrat ion via the drinking water were fourfold higher for enrofloxacin (0.52 +/- 0.16 mu g/mL) compared to danofloxacin (0.12 +/- 0.01 mu g/mL). The steady- state AUC(0-24h) Values of 12.48 and 2.88 mu g.h/mL, respectively, derived from these plasma concentrations are comparable with corresponding area und er the plasma concentration-time curve (AUC) values after single oral admin istration. For both drugs, tissue concentrations markedly exceeded plasma c oncentrations, e.g. in the target lung, tissue concentrations of 0.31 +/- 0 .07 mu g/g for danofloxacin and 0.88 +/- 0.24 mu g/g for enrofloxacin were detected. Taking into account the similar in vitro activity of danofloxacin and enrofloxacin against important pathogens in chickens, a higher therape utic efficacy of water medication for enrofloxacin compared to danofloxacin can be expected when given at the approved dosages.