Clinical Efficacy and Residue Depletion of 10% Enrofloxacin Enteric-Coated Granules in Pigs

Lei, Zhixin; Liu, Qianying; Yang, Bing; Xiong, Jincheng; Li, Kun; Ahmed, Saeed; Hong, Liping; Chen, Pin; He, Qigai; Cao, Jiyue

doi:10.3389/fphar.2017.00294

Cited by 15 publications

(22 citation statements)

References 54 publications

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“…The proposed methods of HPLC were suitable for MBF quantification in plasma and ileum content. These showed specificity and recovery ratios of over 92% in the plasma and 84% in the ileum content, in accordance with the veterinary drug residue guidelines of the Agriculture department and United States Pharmacopeia ( Gad, 2014 ; Lei et al, 2017b ), with a good linear relationship from 0.05 to 20 μg/ml. The chromatograms in Figures 4A,B showed the blank Figure 4A 1 , LLOQ Figure 4A 2 and measured samples Figure 4A 3 in plasma, and blank Figure 4B 1 , LLOQ Figure 4B 2 , and measured samples Figure 4B 3 in ileum content, respectively.…”

Section: Resultssupporting

confidence: 79%

Pharmacokinetic and Pharmacodynamic Evaluation of Marbofloxacin and PK/PD Modeling against Escherichia coli in Pigs

et al. 2017

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The aim of this study was to evaluate the activity of marbofloxacin and establish the optimal dose regimens for decreasing the development of fluoroquinolone resistance in pigs against Escherichia coli with ex vivo pharmacokinetic/pharmacodynamic (PK/PD) modeling. The recommended dose (2 mg/kg body weight) of marbofloxacin was orally administered in healthy pigs. The ileum content and plasma were both collected for the determination of marbofloxacin. The main parameters of Cmax, AUC0-24 h, AUC, Ke, t1/2ke, MRT and Clb were 11.28 μg/g, 46.15, 77.81 μg⋅h/g, 0.001 h-1, 69.97 h, 52.45 h, 0.026 kg/h in ileum content, and 0.55 μg/ml, 8.15, 14.67 μg⋅h/ml, 0.023 h-1, 30.67 h, 34.83 h, 0.14 L/h in plasma, respectively In total, 218 E. coli strains were isolated from most cities of China. The antibacterial activity in vitro and ex vivo of marbofloxacin against E. coli was determined following CLSI guidance. The MIC90 of sensitive strains (142) was calculated as 2 μg/ml. The minimum inhibitory concentration (MIC) of HB197 was 2 and 4 μg/ml in broth and ileum fluids, respectively. In vitro mutant prevention concentration, growth and killing-time in vitro and ex vivo of marbofloxacin against selected HB197 were assayed for pharmacodynamic studies. According to the inhibitory sigmoid Emax modeling, the value of AUC0-24 h/MIC produced in ileum content was achieved, and bacteriostatic, bactericidal activity, and elimination were calculated as 16.26, 23.54, and 27.18 h, respectively. Based on Monte Carlo simulations to obtain 90% target attainment rate, the optimal doses to achieve bacteriostatic, bactericidal, and elimination effects were 0.85, 1.22, and 1.41 mg/kg.bw for 50% target, respectively, and 0.92, 1.33, and 1.53 mg/kg.bw for 90% target, respectively, after oral administration. The results in this study provided a more optimized alternative for clinical use and demonstrated that the dosage 2 mg/kg of marbofloxacin by oral administration could have an effect on bactericidal activity against E. coli.

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Section: Resultssupporting

confidence: 79%

Pharmacokinetic and Pharmacodynamic Evaluation of Marbofloxacin and PK/PD Modeling against Escherichia coli in Pigs

et al. 2017

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“…The cumulative counts for MIC data, with the exception of one resistant strain with an MIC of 256 μg/ml, were performed to match a suitably shaped normal distribution (normality test, P > 0.200) using SigmaStat and GraphPad Prism software (Figure 3 ). Furthermore, the strain whose MIC was 256 μg/ml had been proved as resistant one, with a resistant HAPS_RS04930 reported by Zhixin Lei [ 49 , 50 ]. The optimum MIC range from 0.002 to 32 μg/ml was obtained from non-linear regression (Table 1 ), and the range was further corrected to 0.032 to 32 μg/ml according to the optimum distribution determined using the NORMINV function in Microsoft Excel.…”

Section: Resultsmentioning

confidence: 99%

“…The high MIC value (256 μg/ml) may be explained by cross-resistance of macrolides, exposure to precursors of tildipirosin (tylosin and tilmicosin) or misuse of tildipirosin. The resistance mechanism of HPS to tildipirosin or other macrolides may be associated with the pathways of amino acid ATP-binding cassette (ABC) transporter system (HAPS_2069, HAPS_RS03630) and the metabolite transporter superfamily (HAPS_2067 and HAPS_2068, HAPS_RS08950) [ 49 , 50 , 55 , 56 ], which will be a focus of future studies. Hence, all HPS isolates (163) except one (256 μg/ml) tested in this study could be considered as a WT isolates for ECV.…”

Section: Discussionmentioning

confidence: 99%

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The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin against Haemophilus parasuis

et al. 2017

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The goal of this study was to establish the epidemiological, pharmacodynamic cut-off values, optimal dose regimens for tildipirosin against Haemophilus parasuis. The minimum inhibitory concentrations (MIC) of 164 HPS isolates were determined and SH0165 whose MIC (2 μg/ml ) were selected for PD analysis. The ex vivo MIC in plasma of SH0165 was 0.25 μg/ml which was 8 times lower than that in TSB. The bacteriostatic, bactericidal and elimination activity (AUC24h/MIC) in serum were 26.35, 52.27 and 73.29 h based on the inhibitory sigmoid Emax modeling. The present study demonstrates that 97.9% of the wild-type (WT) isolates were covered when the epidemiological cut-off value (ECV) was set at 8 μg/ml. The parameters including AUC24h, AUC, T1/2, Cmax, CLb and MRT in PELF were 19.56, 60.41, 2.32, 4.02, 56.6, and 2.63 times than those in plasma, respectively. Regarding the Monte Carlo simulation, the COPD was defined as 0.5 μg/ml in vitro, and the optimal doses to achieve bacteriostatic, bactericidal and elimination effect were 1.85, 3.67 and 5.16 mg/kg for 50% target, respectively, and 2.07, 4.17 and 5.78 mg/kg for 90% target, respectively. The results of this study offer a more optimised alternative for clinical use and demonstrated that 4.17 mg/kg of tildipirosin by intramuscular injection could have an effect on bactericidal activity against HPS. These values are of great significance for the effective treatment of HPS infections, but it also be deserved to be validated in clinical practice in the future research.

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“…Susceptibility detection (MIC) for MBF against SS was conducted with the agar dilution method which was based on the guidance of CLSI ( Jorgensen, 1993 ; Lei et al, 2017c ). The strains (2–4 μl) with 10 8 CFU/ml were inoculated into TSA including 5% newborn calf serum, with two-fold serial dilutions of marbofloxacin (0.125–64 μg/ml).…”

Section: Methodsmentioning

confidence: 99%

PK-PD Analysis of Marbofloxacin against Streptococcus suis in Pigs

et al. 2017

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Marbofloxacin is a fluoroquinolone antibiotic and highly effective treatment for respiratory diseases. Here we aimed to evaluate the ex vivo activity of marbofloxacin against Streptococcus suis in pig serum, as well as the optimal dosages scheme for avoiding the fluoroquinolone resistance development. A single dose of 8 mg/kg body weight (bw) was administrated orally to healthy pigs and serum samples were collected during the next 72 h. Serum marbofloxacin content was determined by high-performance liquid chromatography. We estimated the Cmax (6.28 μg/ml), AUC0-24 h (60.30 μg.h/ml), AUC0-∞ (88.94 μg.h/ml), T1/2ke, (12.48 h), Tmax (0.75 h) and Clb (0.104 L/h) of marbofloxacin in pigs, as well as the bioavailability of marbofloxacin (94.21%) after a single 8 mg/kg oral administration. We also determined the pharmacodynamic of marbofloxacin against 134 Streptococcus suis strains isolated from Chinese cities in TSB and serum. These isolated strains had a MIC90 of 1 μg/ml. HB2, a virulent, serotype 2 isolate of SS, was selected for having antibacterial activity in TSB and serum to marbofloxacin. We determined the minimum inhibitory concentration (MIC, 1 μg/ml in TSB, 2 μg/ml in serum), minimum bactericidal concentration (MBC, 4 μg/ml in TSB, 4 μg/ml in serum), and mutant prevention concentration (2.56 μg/ml in TSB) for marbofloxacin against Streptococcus suis (HB2). In serum, by inhibitory sigmoid Emax modeling, the AUC0-24h/MIC values for marbofloxacin against HB2 were 25.23 (bacteriostatic), 35.64 (bactericidal), and 39.71 (elimination) h. Based on Monte Carlo simulations, the predicted optimal oral doses of marbofloxacin curing Streptococcus suis were 5.88 (bacteriostatic), 8.34 (bactericidal), and 9.36 (elimination) mg/kg.bw for a 50% target attainment ratio, and 8.16 (bacteriostatic), 11.31 (bactericidal), and 12.35 (elimination) mg/kg.bw for a 90% target attainment ratio. The data presented here provides optimized dosage information for clinical use; however, these predicted dosages should also be validated in clinical practice.

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Clinical Efficacy and Residue Depletion of 10% Enrofloxacin Enteric-Coated Granules in Pigs

Cited by 15 publications

References 54 publications

Pharmacokinetic and Pharmacodynamic Evaluation of Marbofloxacin and PK/PD Modeling against Escherichia coli in Pigs

Pharmacokinetic and Pharmacodynamic Evaluation of Marbofloxacin and PK/PD Modeling against Escherichia coli in Pigs

The pharmacokinetic-pharmacodynamic modeling and cut-off values of tildipirosin against Haemophilus parasuis

PK-PD Analysis of Marbofloxacin against Streptococcus suis in Pigs

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