Pharmacokinetics and Bioavailability of Florfenicol Following Intravenous, Intramuscular and Oral Administrations in Rabbits

Abstract

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%.

Pharmacokinetics of florfenicol following intravenous and intramuscular administration in dogs

“…injection of florfenicol, the elimination half-life (t ½b ) of the drug in the plasma of dogs was calculated in the present study to be 3.09 h. This finding was in agreement with the time of 3.2 h reported in cattle (Bretzlaff et al1987), 2.87-3.18 h in calves (Varma et al 1986;Adams et al 1987;Decraene et al 1997), 2.61 h in goats (Atef et al 2001) and 3.02 h in broiler chickens (Shen et al 2003). However, this value (3.09 h) was also much longer than those reported in several previous studies: 1.1 h in dogs (Park et al 2008), 1.49 h in camels (Ali et al 2003), 1.31-1.09 h in sheep (Ali et al 2003;Lane et al 2004), 1.80 h in equines (McKellar and Varma 1996) and 1.54-0.90 h in rabbits (Abd El- Aty et al 2004;Park et al 2007). Differences in kinetic parameters are relatively common, and frequently related to interspecies variation, age, breed, health status of the animals and/or the assay method used.…”

“…was 44.70 ± 6.75%. The doi: 10.17221/8247-VETMED value was similar to that recorded for florfenicol in lactating cows (38%; Soback et al 1995), while higher than that for chloramphenicol in cattle (19%; Sanders et al 1988) and lower than that recorded for florfenicol in rabbits (Abd El-Aty et al 2004), sheep (Jianzhong et al 2004), goats (Atef et al 2001). This difference in bioavailability from the intramuscular site might be due to differences in regional blood flow from muscle tissues.…”

“…administration can be considered as representing a 'flip-flop' situation. The commercially available formulation of florfenicol is long-acting, so that "flip-flop" kinetics occurred, where elimination is prolonged due to slow absorption from the injection site (Abd El-Aty et al 2004;Switala et al 2007). The absorption of florfenicol after intramuscular administration appeared slow and the kinetic parameters and serum concentration time curve were suggestive of absorption rate-dependent elimination (Soback et al 1995).…”

Influences of flunixin and tenoxicam on the pharmacokinetics of florfenicol in lipopolysaccharide-induced endotoxemia

“…However, this value slightly increased in coadministration of FF-FM-LPS and FF-TN-LPS when compared with FF-LPS in animal groups. As a result, increasing the AUC (0)(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and lengthening the t 1/2λz may be related to decreasing the Cl T of FF in coadministered groups in endotoxemic rabbits. In our study, the V ss of FF was large (from 1.85 ± 0.12 to 2.21 ± 0.06 L/kg).…”

“…This situation may be the result of various processes that may include alterations in the pharmacokinetics of the drug (9). Until now, the pharmacokinetic disposition of FF has been extensively documented in healthy and infected animal species only when FF was administered alone (10)(11)(12)(13)(14). Interactions of FF with some drugs (anthelmintics, polyether ionophores, and tylosin) have been reported in previous studies (15)(16)(17).…”