Comparative pharmacokinetics of two florfenicol formulations following intramuscular and subcutaneous administration to sheep

Abstract

OBJECTIVE To compare the pharmacokinetics of 2 commercial florfenicol formulations following IM and SC administration to sheep. ANIMALS 16 healthy adult mixed-breed sheep. PROCEDURES In a crossover study, sheep were randomly assigned to receive florfenicol formulation A or B at a single dose of 20 mg/kg, IM, or 40 mg/kg, SC. After a 2-week washout period, each sheep was administered the opposite formulation at the same dose and administration route as the initial formulation. Blood samples were collected immediately before and at predetermined times for 24 hours after each florfenicol administration. Plasma florfenicol concentrations were determined by high-performance liquid chromatography. Pharmacokinetic parameters were estimated by noncompartmental methods and compared between the 2 formulations at each dose and route of administration. RESULTS Median maximum plasma concentration, elimination half-life, and area under the concentration-time curve from time 0 to the last quantifiable measurement for florfenicol were 3.76 μg/mL, 13.44 hours, and 24.88 μg•h/mL, respectively, for formulation A and 7.72 μg/mL, 5.98 hours, and 41.53 μg•h/mL, respectively, for formulation B following administration of 20 mg of florfenicol/kg, IM, and 2.63 μg/mL, 12.48 hours, and 31.63 μg•h/mL, respectively, for formulation A and 4.70 μg/mL, 16.60 hours, and 48.32 μg•h/mL, respectively, for formulation B following administration of 40 mg of florfenicol/kg, SC. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that both formulations achieved plasma florfenicol concentrations expected to be therapeutic for respiratory tract disease caused by Mannheimia haemolytica or Pasteurella spp at both doses and administration routes evaluated.

Comparative muscle irritation and pharmacokinetics of florfenicol-hydroxypropyl-β-cyclodextrin inclusion complex freeze-dried powder injection and florfenicol commercial injection in beagle dogs

“…On the basis of our research, the average drug loading is 11.78% ± 0.04%. Moreover, the prepared FF-HP-β-CD was observed to have a highly enhanced solubility of 78.93 ± 0.42 mg/mL at 37 °C, which is 35.4-fold compared with FF (2.23 ± 0.04 mg/mL) and is more than the reported solubility of 40.76 mg/mL 9 .…”

“…The pharmacokinetics of FF has been previously studied in animal species, including rabbits, rats, dogs, carp, swine, and sheep 9,14–17 Species differences in FF elimination exist. One-compartment open, two-compartment open, and non-compartment models exist after intravenous, intramuscular, and oral administrations in different species 18,19 .…”

“…Twelve beagle dogs were randomly divided into two groups. The control group was administered with 10% FF injection, whereas the other was administered with FF-HP-β-CD aqueous solution at the left hind limb muscle (20 mg FF/kg body weight) 9,14 . At predetermined time points, blood samples were collected from the auricular vein.…”

Borneol influences the pharmacokinetics of florfenicol through regulation of cytochrome P450 1A2 (CYP1A2), CYP2C11, CYP3A1, and multidrug resistance 1 (MDR1) mRNA expression levels in rats

“…Florfenicol has less toxicity and better antibacterial activity than chloramphenicol or thiamphenicol [4,11,24]. The pharmacokinetic properties of florfenicol have been documented in many animal species [1,2,9,22,28,30], and several studies have reported on the possible metabolic pathways and mechanisms of florfenicol in vivo. Liu et al [18] reported that P-gp and/or cytochrome P450 3A (CYP3A) are likely involved in the distribution of florfenicol in rabbits.…”

Effects of anemoside B4 on pharmacokinetics of florfenicol and mRNA expression of CXR, MDR1, CYP3A37 and UGT1E in broilers

“…Florfenicol has low toxicity and better antibacterial activity than does chloramphenicol or thiamphenicol [3,12,25]. The pharmacokinetics of florfenicol has been documented in many animal species [1,2,6,22,29,32]. A few studies have also reported on the possible metabolic pathways and mechanisms of florfenicol in vivo.…”