AUTHOR=Bonassa Karina P. D. , Miragliotta Miwa Y. , Simas Rosineide C. , Eberlin Marcos N. , Anadón Arturo , Moreno Ronilson A. , Reyes Felix G. R. 

TITLE=Pharmacokinetics, Pharmacodynamic Efficacy Prediction Indexes and Monte Carlo Simulations of Enrofloxacin Hydrochloride Against Bacterial Strains That Induce Common Clinical Diseases in Broiler Chickens

JOURNAL=Frontiers in Veterinary Science

VOLUME=7

YEAR=2021

URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2020.606872

DOI=10.3389/fvets.2020.606872

ISSN=2297-1769

ABSTRACT=<p>Pharmacokinetic parameters and efficacy prediction indexes (C<sub>max</sub>/MIC<sub>90</sub> and AUC<sub>0−24</sub>/MIC<sub>90</sub>) of an enrofloxacin hydrochloride (ENR-HCl) veterinary product soluble in water were determined in healthy broiler chickens of both sexes after a single oral dose of ENR-HCl (equivalent to 10 mg ENR base/kg bw). Monte Carlo simulations targeting C<sub>max</sub>/MIC<sub>90</sub> = 10 and AUC<sub>0−24</sub>/MIC<sub>90</sub> =125 were also performed based on a set of MIC (minimum inhibitory concentration) values of bacterial strains that induce common clinical diseases in broiler chickens and that showed to be susceptible to ENR-HCl. Plasma concentrations of ENR and its main metabolite ciprofloxacin (CIP) were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma concentration-time curves were found to fit a non-compartmental open model. The ratio of the area under the plasma concentration-time curve (AUC) of CIP/ENR was 4.91%. Maximum plasma concentrations of 1.35 ± 0.15 μg/mL for ENR-HCl and 0.09 ± 0.01 μg/mL for CIP were reached at 4.00 ± 0.00 h and 3.44 ± 1.01 h, respectively. Areas under the plasma vs. time concentration curve in 24 h (AUC<sub>0−24</sub>) were 18.91 ± 1.91 h × μg/mL and 1.19 ± 0.12 h × μg/mL for ENR-HCl and CIP, respectively. Using a microbroth dilution method, the minimum inhibitory concentration (MIC<sub>90</sub>) values were determined for ENR-HCl for 10 bacterial strains (<italic>Mycoplasma gallisepticum, Mycoplasma synoviae, Avibacterium paragallinarum, Clostridium perfringens, Escherichia coli, Pseudomonas aeruginosa, Salmonella</italic> ser. Enteritidis<italic>, Salmonella</italic> ser. Gallinarum<italic>, Salmonella</italic> ser. Pullorum, and <italic>Salmonella</italic> ser. Typhimurium), which are the most common causes of infectious clinical diseases in broiler chickens. In summary, the PK/PD ratios and Monte Carlo simulation were carried out for ENR-HCl in poultry, which due to its solubility was administered in drinking water. The PK/PD efficacy prediction indexes and Monte Carlo simulations indicated that the ENR-HCl oral dose used in this study is useful for bacterial infections in treating <italic>C. perfringens</italic> (Gram-positive), <italic>E. coli</italic> and <italic>S</italic>. ser. Enteritidis (Gram-negative) and <italic>M. gallisepticum</italic> bacteria responsible for systemic infections in poultry, predicting a success rate of 100% when MIC ≤ 0.06 μg/mL for <italic>E. coli</italic> and <italic>S</italic>. ser. Enteritidis and MIC ≤ 0.1 μg/mL for <italic>M. gallisepticum</italic>. For <italic>C. perfringens</italic>, the success rate was 98.26% for MIC ≤ 0.12. However, clinical trials are needed to confirm this recommendation.</p>