Intravenous and subcutaneous pharmacokinetics of florfenicol in sheep

Abstract

Pharmacokinetic parameters of florfenicol were determined in 10 adult sheep (five wethers and five ewes) after a single 40 mg/kg intravenous (i.v.) dose, and three daily subcutaneous (s.c.) doses of 40 mg/kg of a commercial preparation (Nuflor((R))). The concentration of florfenicol in serum samples was assayed using a proprietary HPLC assay method, and pharmacokinetic parameters derived for individual animal data by each route using compartmental and noncompartmental approaches. Two animals (one male and one female) were excluded due to observed i.v. dosing problems, and a biexponential model was found to fit the i.v. data well for six of the other eight animals. Data from two males showed prolonged low concentrations of florfenicol in serum and were better fit by a three-compartment model. The mean +/- SD for the half-lives of the distribution and elimination phases for the six sheep best fit with a two-compartment model were 0.069 +/- 0.018 and 1.01 +/- 0.09 h respectively, and for the V(d(ss)) and clearances were 0.503 +/- 0.035 L/kg and 366 +/- 53 mL/h/kg respectively. The data collected during the s.c. multiple dose study were analyzed using noncompartmental methods only. The bioavailability (F%) after s.c. dosing was calculated in three ways to compare estimation methods as steady-state had not been reached and single dose s.c. data were not obtained past 24 h. Using the AUC(0--24) and AUC(0--> infinity ) from the first dose, the F% values averaged 27 and 40% respectively. Using the AUC(0--> infinity ) for all doses, the F% was 65%. Calculations of the mean time during which the serum concentration exceeded 0.5 and 1.0 microg/mL were 105 +/- 3.9 and 74.7 +/- 12.2 h respectively.

Pharmacokinetics of florfenicol following intravenous and intramuscular administration in dogs

“…in dogs were best fitted to a two compartment open model. These results are in agreement with the findings of previous studies on florfenicol performed in sheep (Ali et al 2003;Lane et al 2004), goats (Atef et al 2001;Ali et al 2003), calves (Varma et al 1986;Adams et al 1987;Decraene et al 1997) and broiler chickens (Shen et al 2003). However, Lobell et al (1994), Soback et al (1995) and Jianzhong et al (2004) found that the disappearance of florfenicol from the plasma after i.v.…”

“…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.…”

“…The pharmacokinetics of florfenicol have been extensively investigated in veal calves (Varma et al 1986;Adams et al 1987), cows (Bretzlaff et al 1987;Soback et al 1995), horses (McKellar and Varma 1996), goats (Atef et al 2001), broiler chickens (Shen et al 2002), pigs (Liu et al 2003), camels (Ali et al 2003) North American elk (Alcorn et al 2004), sheep (Lane et al 2004;Jianzhong et al 2004), catfish (Park et al 2006) and rabbits (Park et al 2007). However, florfenicol pharmacokinetics in dogs have scarcely been documented (Park et al 2008, Kim et al2011.…”

Florfenicol concentrations in milk of lactating cows postreated by intramuscular or intramammary routes

“…respectively (9,13). Another study in sheep in 2004 found Vd=0.55L/Kg (14). These Vds could indicate a good milk excretion.…”

Pharmacokinetics and Bioequivalence of Florfenicol Oral Solution Formulations (Flonicol® and Veterin®10%) in Broiler Chickens

“…The HPLC and extraction procedures were modified from previously published methods [24,25]. The HPLC system consisted of a pump (LC-10A DVP) with UV-vis detector (SPD-10 AVP), auto injector (SIL-10A DVP), solvent degasser (DGV-12 A) and Shimadzu class-VP software (Ver 6.12 SP4) (Shimadzu, Japan).…”