The influence of rapid growth in broilers on florfenicol pharmacokinetics – allometric modelling of the pharmacokinetic and haemodynamic parameters

The pharmacokinetics of florfenicol (FF) and thiamphenicol (TP) after single intravenous (IV) and oral (PO) administration was investigated in Mulard ducks. Both antibiotics were administered at a dose of 30 mg/kg body weight, and their concentrations in plasma samples were assayed using high‐performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were calculated using a noncompartmental method. After IV administration, significant differences were found for the mean residence time (2.25 ± 0.21 hr vs. 2.83 ± 0.50 hr for FF and TP, respectively) and the general half‐life (1.56 ± 0.15 hr vs. 1.96 ± 0.35 hr for FF and TP, respectively) indicating slightly slower elimination of TP as compared to FF. The clearance, however, was comparable (0.30 ± 0.07 L/hr/kg for FF and 0.26 ± 0.04 L/hr/kg for TP). The mean volume of distribution was below 0.7 L/kg for both drugs. Pharmacokinetics after PO administration was very similar for FF and TP suggesting minor clinical importance of the differences found in the IV study. Both antimicrobials showed rapid absorption and bioavailability of more than 70% indicating that PO route should be an efficient method of FF and TP administration to ducks under field conditions.

Section: Pharmacokinetic Parameters (Mean ± Sd) In Ducks After Singlementioning

confidence: 81%

Pharmacokinetics of florfenicol and thiamphenicol in ducks

Tikhomirov

Poźniak

Smutkiewicz

et al. 2018

“…Furthermore, based on its low toxicity, high bioavailability (near to 100%), and the therapeutic effect equal to or better than other chloramphenicol analogs, FF is recommended to treat for intestinal tract and respiratory infectious diseases in livestock (Kim et al., ; Liu, Fung, Chen, Zeng, & Zhang, ; Ueda, Ohtsuki, & Narukawa, ). There are several previously published reports on the pharmacokinetics (PK) and pharmacodynamics (PD) of FF in the serum in vitro in the chicken, pigs, dogs, and so on (Burch & Klein, ; Dorey, Pelligand, Cheng, & Lees, ; Haritova & Fink‐Gremmels, ; Koc et al., ; Lei, Liu, Qi, et al., ; Lei, Liu, Yang, Ahmed, et al., ; Lei, Liu, Yang, Yang, et al., ; Lei, Liu, Zhu, et al., ; Maaland, Mo, Schwarz, & Guardabassi, ; Poźniak et al., ; Sidhu, Illambas, Potter, Rycroft, & Lees, ; Wang et al., ). However, it is insufficient to assay the practical effect and predict the dosage accordingly with serum and in vitro PK‐PD data.…”

Section: Introductionmentioning

confidence: 99%

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

Lei

Liu

Khaliq

et al. 2019

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.

“…The distribution and elimination half‐lives, 0.132 ± 0.0289 hr and 2.78 ± 0.166 hr, were in agreement with results previously reported in pigs (Liu et al., ). Fast elimination was also observed in other species of animals, dog 3.09 ± 0.13 hr (Birdane & Birdane, ), chicken 0.73 ± 0.08 to 1.07 ± 0.07 hr (Poźniak et al., ), llamas 2.2 hr (Pentecost, Niehaus, Werle, & Lakritz, ), rabbit 2.69 ± 0.38 hr (Koç, Atila, Karakuş, & Üney, ), sheep 1.01 ± 0.09 hr (Lane et al., ), respectively.…”

Section: Discussionmentioning

confidence: 77%

Bayesian population pharmacokinetic modeling of florfenicol in pigs after intravenous and intramuscular administration

Liu

Rong

Zeng

et al. 2018

Bayesian population pharmacokinetic models of florfenicol in healthy pigs were developed based on retrospective data in pigs either via intravenous (i.v.) or intramuscular (i.m.) administration. Following i.v. administration, the disposition of florfenicol was best described by a two-compartment open model with the typical values of half-life at α phase (t ), half-life at β phase (t ), total body clearance (Cl), and volume of distribution (V ) were 0.132 ± 0.0289, 2.78 ± 0.166 hr, 0.215 ± 0.0102, and 0.841 ± 0.0289 L kg , respectively. The disposition of florfenicol after i.m. administration was best described by a one-compartment open model. The typical values of maximum concentration of drug in serum (C ), elimination half-life (t ), Cl, and Volume (V) were 5.52 ± 0.605 μg/ml, 9.96 ± 1.12 hr, 0.228 ± 0.0154 L hr kg , and 3.28 ± 0.402 L/kg, respectively. The between-subject variabilities of all the parameters after i.m. administration were between 25.1%-92.1%. Florfenicol was well absorbed (94.1%) after i.m. administration. According to Monte Carlo simulation, 8.5 and 6 mg/kg were adequate to exert 90% bactericidal effect against Actinobacillus pleuropneumoniae after i.v. and i.m. administration.