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

Pharmacokinetic parameters and efficacy prediction indexes (C _max /MIC ₉₀ and AUC _0-24 /MIC ₉₀ ) 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 _max /MIC ₉₀ = 10 and AUC _0-24 /MIC ₉₀ =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 _0-24 ) 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 ₉₀ ) values were determined for ENR-HCl for 10 bacterial strains ( Mycoplasma gallisepticum, Mycoplasma synoviae, Avibacterium paragallinarum, Clostridium perfringens, Escherichia coli, Pseudomonas aeruginosa, Salmonella ser. Enteritidis , Salmonella ser. Gallinarum , Salmonella ser. Pullorum, and Salmonella 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 C. perfringens (Gram-positive), E. coli and S . ser. Enteritidis (Gram-negative) and M. gallisepticum bacteria responsible for systemic infections in poultry, predicting a success rate of 100% when MIC ≤ 0.06 μg/mL for E. coli and S . ser. Enteritidis and MIC ≤ 0.1 μg/mL for M. gallisepticum . For C. perfringens , the success rate was 98.26% for MIC ≤ 0.12. However, clinical trials are needed to confirm this recommendation.
Competing Interests: MM was employed by company AGRIAS Pesquisa & Desenvolvimento S.A.R.C. no Agronegócio Ltda., Amparo, Brazil. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Bonassa, Miragliotta, Simas, Eberlin, Anadón, Moreno and Reyes.)