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J Vet Pharmacol Ther. 2019 May;42(3):324-335. doi: 10.1111/jvp.12754. Epub 2019 Feb 22.

Resistant cutoff values and optimal scheme establishments for florfenicol against Escherichia coli with PK-PD modeling analysis in pigs.

Lei Z1,2,3,4, Liu Q1,2,3, Khaliq H2,3, Cao J1,2, He Q1,2.

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State Key Laboratory of Agriculture Microbiology, College of Veterinary Medicine, Huazhong Agriculture University, Wuhan, China.
Department of Veterinary Pharmacology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agriculture University, Wuhan, China.
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota.


Florfenicol, a structural analog of thiamphenicol, has broad-spectrum antibacterial activity against gram-negative and gram-positive bacteria. This study was conducted to investigate the epidemiological, pharmacokinetic-pharmacodynamic cutoff, and the optimal scheme of florfenicol against Escherichia coli (E. coli) with PK-PD integrated model in the target infectious tissue. 220 E. coli strains were selected to detect the susceptibility to florfenicol, and a virulent strain P190, whose minimum inhibitory concentration (MIC) was similar to the MIC50 (8 μg/ml), was analyzed for PD study in LB and ileum fluid. The MIC of P190 in the ileum fluid was 0.25 times lower than LB. The ratios of MBC/MIC were four both in the ileum and LB. The characteristics of time-killing curves also coincided with the MBC determination. The recommended dosages (30 mg/kg·body weight) were orally administrated in healthy pigs, and both plasma and ileum fluid were collected for PK study. The main pharmacokinetics (PK) parameters including AUC24 hr , AUC0-∞ , Tmax , T1/2 , Cmax , CLb, and Ke were 49.83, 52.33 μg*h/ml, 1.32, 10.58 hr, 9.12 μg/ml, 0.50 L/hr*kg, 0.24 hr-1 and 134.45, 138.71 μg*hr/ml, 2.05, 13.01 hr, 16.57 μg/ml, 0.18 L/hr*kg, 0.14 hr-1 in the serum and ileum fluid, respectively. The optimum doses for bacteriostatic, bactericidal, and elimination activities were 29.81, 34.88, and 36.52 mg/kg for 50% target and 33.95, 39.79, and 42.55 mg/kg for 90% target, respectively. The final sensitive breakpoint was defined as 16 μg/ml. The current data presented provide the optimal regimens (39.79 mg/kg) and susceptible breakpoint (16 μg/ml) for clinical use, but these predicted data should be validated in the clinical practice.


E. coli ; cutoff; florfenicol; pharmacokinetic-pharmacodynamic; pigs

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