Studies On The Post-antibiotic Effects And Pharmacokinetics Of Florfenicol In Chicken

Florfenicol, a fluorinated analogue of thiamphenicol and chloramphenicol, is a synthetic, broad-spectrum antibiotic specially for veterinary use. Its structural modification confers advantages in antibacterial activity, particularly against pathogenic bacteria resistant to thiamphenicol and chloramphenicol. For its widely used in the future, PAE and pharmacokmetics of florfenicol were studied.The antibacterial activity of 9 kinds of antimicrobial agents against Pasteurella multocida (462 C48-11) in vitro was studied. And the post-antibiotic effects (PAEs), post-antibiotic Sub-MIC effects (PA-SMEs) and Sub-MIC effects (SMEs) of florfenicol against P. multocida were observed. The infected tissue cage models, for determining PAEs in vivo of florfenicol, had been developed in chickens. Florfenicol was orally administed to investigate its pharmacokinetic characteristics by using bioassay.Minimal inhibitory concentration (MIC) of Ampicillin, Amoxicillin, Kanamycin, Oxytetracycline, Doxycycline, Thiamphenical, Florfenicol, Tilmicosin, Norfloxacin against P. multocida was detected by the two-fold dilution method in vitro. The results showed that MICs were 0.125, 0.125, 2, 128, 32, 8, 0.5, 2 and 0.125μg/mL, respectively.Florfenicol was exposured to P. multocida for 1 to 2h and removed, the viable bacteria were counted according to its growth on agar plate. PAEs, PA-SMEs and SMEs of florfenicol ranged from 0.18 to 5.87h, from 1.66h to 24.2h and from 0.05 to 1.31h. The results showed that PAEs were positively related to the drug concentrations in 2-8MIC and the time exposure to the bacteria, but negetively to the inoculum size. The results of florfenicol demonstrated that PA-SMEs were longer than PAEs in the same inducement concentration.The infected tissue cage model, developed by implanting two plastic tissue cages in chicken's subcutaneous tissue, was used to determine PAEs of florfenicol against P. multocida in vivo after the exposure to the drug in vitro for lh. The results showed that PAEs of 4MIC and 8MIC were 1.20 and 1.48h in vivo, 0.93 and 1.17h in vitro, respectively.The pharmacokinetics showed that the concentration course of florfenicol in serum following its oral administration (30mg/kg) in chicken can be described by one-compartment open model with first-order absorption. The equation was shown below: C=4.7804(e⁰.1096t-e^-2.5858t). The primary parameters were as follows: t₁/2Ka 0.28±0.07h, 6.42±0.83h, tmax 1.32±0.26h, Cmax 3.96±0.42ug/mL, AUC 42.41 ±7.50 (μg/mL)h.The results showed that florfenicol is can be absorbed quickly, the elimination half life is long.Binding the pharmacokinetic characteristics of florfenicol following its oral administration and the PAE in vitro and in vivo, the ideal dosage regime is suggested that chicken can take florfenicol once daily with oral administration of 30mg/kg b.w..