Pharmacokinetics and tissue disposition of danofloxacin in sheep

Abstract

The plasma pharmacokinetics of danofloxacin administered at 1.25 mg kg(-1) body weight by the intravenous and intramuscular routes were determined in sheep. Tissue distribution was also determined following administration by the intramuscular route at 1.25 mg kg(-1) body weight. Danofloxacin had a large volume of distribution at steady state (V-dss) of 2.76 +/- 0.16 h (mean +/- S.E.M.) L kg(-1), an elimination half-life ((1/2 beta)) of 335 +/- 0.23 h, and a body clearance (C1) of 0.63 +/- 0.04 L kg(-1) h(-1). Following intramuscular administration it achieved a maximum concentration (C-max) of 0.32 +/- 0.02 mu g mL(-1) at 1.23 +/- 0.34 h (t(max)) and had a mean residence time (MRT) of 5.45 +/- 0.19 h. Danofloxacin had an absolute bioavailability (F) of 95.71 +/- 4.41% and a mean absorption time (MAT) of 0.81 +/- 0.20 h following intramuscular administration. Mean plasma concentrations of > 0.06 mu g mL(-1) were maintained for more than 8 h following intravenous and intramuscular administration. Following intramuscular administration highest concentrations were measured in plasma (0.43 +/- 0.04 mu g mL(-1)), lung (1.51 +/- 0.18 mu g g(-1)), and interdigital skin (0.64 +/- 0.18 mu g g(-1)) at 1 h, duodenal contents (0.81 +/- 0.40 mu g mL(-1)), lymph nodes (4.61 +/- 0.35 mu g g(-1)), and brain (0.06 +/- 0.00 mu g mL(-1)) at 2 h, jejunal (10.50 +/- 4.31 mu g mL(-1)) and ileal (5.25 +/- 1.67 mu g mL(-1)) contents at 4 h, and colonic contents (8.94 +/- 0.65 mu g mL(-1)) at 8 h. (C) 1998 John Wiley & Sons, Ltd.