Pharmacokinetics and bioavailability of florfenicol following intravenous, intramuscular and oral administrations in rabbits.

This study examined the disposition kinetics and bioavailability of florfenicol after intravenous (i.v.), intramuscular (i.m.) and oral administration to rabbits at a dose of 30 mg/kg BW. Serial blood samples were collected through an indwelling catheter intermittently for 24 h for various routes. Plasma antibacterial concentrations were determined using a microbiological assay method with Bacillus subtilis ATCC 6633 as a reference organism. Plasma concentration-time data generated in the present study were analysed by non-compartmental methods based on statistical moment theory. Following i.v. administration, the overall elimination half-life (t1/2beta) was 1.54 h, mean residence time (MRT) was 1.69 h, mean volume of distribution at steady-state (Vdss) was 0.57 L/kg, and total body clearance (Cltot) was 0.34 L/kg/h. After i.m. and oral dosing, the terminal part of the curve should correspond to the absorption phase, instead of to the elimination phase, with terminal half-lives of 3.01 and 2.57 h, respectively. The mean absorption time (MAT) was 2.65 h for i.m. and 2.01 h for oral administration. Elimination rate constants differed with i.v., i.m. and oral administrations, suggesting a flip-flop situation. The observed mean peak plasma concentrations (Cmax obs) were 21.65 and 15.14 microg/ml achieved at a post-injection time (Tmax obs) of 0.5 h following i.m. and oral dosing, respectively. The absolute systemic availabilities were 88.25% and 50.79%, respectively, and the extent of plasma protein binding percent was 11.65%.