Depletion of florfenicol in lactating dairy cows after intramammary and subcutaneous administration

Abstract

Eighteen Holstein dairy cows ranging in body weight from 500-700 kg and with an average milk yield of 37 ± 6 kg/day were used to investigate the depletion of florfenicol (FFL) in milk and plasma of dairy cows. Three groups of six were administered FFL: Group A, intramammary (IMM) infusion of ~2.5 mg FFL/kg BW at three consecutive milking intervals (total amount of ~7.5 mg/kg BW); Group B, one IMM infusion (20 mg/kg BW) into one quarter and Group C, one subcutaneous (SC) treatment (40 mg/kg BW). IMM infusions were into the right front quarter. Cows were milked daily at 06:00 and 18:00 h. The highest concentrations (C ) and time to C (T ) were: 1.6 ± 2.2 μg·FFL/mL milk at 22 h (Group A), 5.5 ± 3.6 μg·FFL/mL milk at 12 h (Group B), and 1.7 ± 0.4 μg·FFL/mL milk at 12 h (Group C). The half-lives (t ) were ~19, 5.5, and 60 h, for Groups A, B, and C, respectively. FFL was below the limit of detection (LOD) by 60 h in three Group B cows, but above the LOD at 72, 84, and 120 h in three cows. FFL was above the LOD in milk from Group C's cows for 432-588 h. Plasma values followed the same trends as milk. The results demonstrate that IMM-infused FFL is bioavailable and below the LOD within 72-120 h. The concentration of FFL was detectable in both plasma and milk over the course of 2-3 weeks after SC administration. The absence of residue depletion data presents problems in determining safe levels of FFL residues in milk and edible tissues. The data presented here must not be construed as approval for extra-label use in food animals.

Comparison of the Intestinal Pharmacokinetics of Two Different Florfenicol Dosing Regimens and Its Impact on the Prevalence and Phenotypic Resistance of E. coli and Enterococcus over Time

“…In pharmacokinetic terms, this is known as the “flip-flop” effect, where the rate of absorption influences the terminal slope of the plasma vs. time profile [ 16 ]. Previous studies have assessed florfenicol plasma drug concentrations in cattle after parenteral administration [ 11 , 12 , 17 , 18 ]. In the study conducted by Gilliam et al, florfenicol was administered in a digital vein for means of regional limb perfusion at a significantly lower dose (2.2 mg/kg).…”

Extralabel drug use in small ruminants

“…Currently, FARAD recommends a 60day meat and 7-day milk WDI for goats administered 2 IM doses of florfenicol (20 mg/kg) separated by a 48-hour interval and a 70-day meat and 26-day milk WDI for goats administered a single SC dose of florfenicol (40 mg/kg); FARAD also recommends that the milk from all treated goats be tested and free of florfenicol and metabolite residues before it is marketed for human consumption. This is especially important after SC administration because results of a study 67 in cattle suggest that florfenicol residues remain detectable in milk for a prolonged period.…”

Comparison of florfenicol depletion in dairy goat milk using ultra-performance liquid chromatography with tandem mass spectrometry and a commercial on-farm test

“…The majority of requests were for WDIs following subcutaneous administration with approximately half of the total submissions requesting milk WDIs. Determining a substantially extended milk WDI is challenging because there is only one published study in lactating dairy cattle following the subcutaneous administration of florfenicol, which reported a 60 h milk half-life and concentrations above the limit of detection up to 588 h after a single 40 mg/kg dose ( 2 ).…”