Pharmacokinetics of danofloxacin 18% in lactating sheep and goats

Abstract

The pharmacokinetics of danofloxacin administered at 6 mg/kg bodyweight by the intravenous and subcutaneous (s.c.) routes were determined in sheep and goats. Milk concentrations were also determined following s.c. administration. Plasma and milk concentrations of danofloxacin were measured using high-performance liquid chromatography. The plasma concentration-time curves were analysed by noncompartmental methods. Danofloxacin had a similar large volume of distribution at steady state in sheep and goats of 2.19 +/- 0.28 and 2.43 +/- 0.13 L/kg, and a similar body clearance of 0.79 +/- 0.15 and 0.98 +/- 0.13 L/kg.h, respectively. Following s.c. administration, danofloxacin achieved a similar maximum concentration in sheep and goats of 1.48 +/- 1.54 and 1.05 +/- 0.09 mg/L, respectively at 1.6 h and had a mean residence time of 4.93 +/- 0.79 and 4.51 +/- 0.44 h, respectively. Danofloxacin had an absolute bioavailability of 93.6 +/- 13.7% in sheep and 97.0 +/- 15.7% in goats and a mean absorption time of 2.07 +/- 0.75 and 2.01 +/- 0.53 h, respectively. Mean danofloxacin concentrations in milk after s.c. administration to sheep were approximately 10 times higher than plasma at 12 h postdose and remained eight times higher at 24 h postdose. In goats, mean concentration of danofloxacin in milk were approximately 13 times higher than plasma at 12 h postdose and remained four times higher at 24 h postdose. Thus, danofloxacin 18% administered s.c. to lactating ewes and goats at a dose rate of 6 mg/kg was characterized by extensive absorption, high systemic availability and high distribution into the udder resulting in higher drug concentrations being achieved in milk than in plasma.