Florfenicol in non‐lactating dairy cows: pharmacokinetics, binding to plasma proteins, and effects on phagocytosis by blood neutrophils

Abstract

Serial blood samples were collected and plasma concentrations of florfenicol (FLO) were measured following the administration of an intravenous bolus of 50 mg/kg FLO to five healthy non-lactating dairy cows. A triexponential equation provided the best fit of the data for four of the five cows. The mean value for beta corresponded to a half-life of 3.2 h. The mean apparent volume of distribution was 0.67 l/kg, and the mean body clearance was 0.15 l/kg/h. The extent of binding of FLO to bovine plasma proteins was determined in vitro at concentrations of 5 micrograms/ml and 50 micrograms/ml by equilibrium dialysis and ultrafiltration. The drug was 18% and 19% bound by equilibrium dialysis, and 23% and 19% bound by ultrafiltration, at 5 micrograms/ml and 50 micrograms/ml, respectively. Phagocytosis of 32phosphorus-labelled Staphylococcus aureus by bovine blood neutrophils was compared in vitro between neutrophils incubated in phosphate-buffered saline alone or in combination with 5, 125, or 1000 micrograms/ml chloramphenicol or FLO. There was no significant effect of chloramphenicol at any concentration. Florfenicol significantly inhibited phagocytosis at all concentrations, but the percentage inhibition was small. The clinical significance, if any, of this effect of FLO remains to be demonstrated.

Pharmacokinetics of florfenicol following intravenous and intramuscular administration in dogs

“…The Cl T was similar to that reported for thiamphenicol in dogs (Castells et al 1998). Bretzlaff et al (1987) suggested that the small Cl of florfenicol in animals is due to the replacement of -OH in chloramphenicol and thiamphenicol by -F in the structure florfenicol, which thereby prevents the conjugation with glucuronic acid and delays its excretion. These little differences may be related to differences in metabolism, analytical methods or the metabolic body size of the animals under study.…”

“…The minimum inhibitory concentrations (MICs) of florfenicol for bacterial isolates from dogs have not yet been determined. Based on the MIC data for bacteria from fish, swine, calves and cows, 1-2 µg/ml florfenicol showed high efficacy against most bacteria (Varma et al 1986;Bretzlaff et al 1987;Ueda et al 1995;Ho et al 2000). In this study, the time of plasma concentration above 1 µg/ml was approximately 8 h. Therefore, florfenicol should be given twice daily at a dosage of 30 mg/kg b.w.…”

“…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.…”

The effects of florfenicol on lymphocyte subsets and humoral immune response in mice

“…Bretzlaff et al (1987) reported a suppressive effect of florfenicol on the activity of neutrophiles. They observed that florfenicol at concentrations within the ranges of 5 to1000 μg/ml of cell culture inhibited phagocytosis of 32 phosphorus-labelled Staphylococcus aureus by bovine blood neutrophils.…”

Tissue pharmacokinetics of florfenicol in pigs experimentally infected with Actinobacillus pleuropneumoniae

“…Afifi et al (1997) found higher concentrations in the lung,liver, kidney, muscle and plasma than that in brain and fat of the broiler following singledose of 3Omg/kg by i.rn, and the FFC became undetectable at 72 h postdose in above tissues except in the bilefrom where it disappeared after 96 h (Afifi and Abo el-Sooud, 1997). Florfenicol appeared to have higher concentrations and AVC in the kidney as it dominated the excretion of florfenicol at a large extent (Varma et al, 1986;Bretzlaff et al, 1987). In most animal species, 80% of florfenicol was excreted from urine as parent drug while 11.2-17% as florfenicol amine, less than 10% as florfenicol oxamic alcohol and 1.1% as florfenicol alcohol according to its determination by radioisotope labellingin the residue report of EMEA (1999) (Committee for veterinary medicinal products, 1999).This metabolic characteristic was similar with thiamphenicol but totally different from CAP, the majority of which was excreted as its derivatives (Syriopoulou et al, 1981).…”