title: Pharmacokinetic and Pharmacodynamic Integration and Modeling of Enrofloxacin in Swine for Escherichia coli.
abstract: The aim of this study was to optimize the dose regimens of enrofloxacin to reduce the development of fluoroquinolone resistance in Escherichia coli (E.coli) using pharmacokinetic/pharmacodynamic (PK/PD) modeling approach. The single dose (2.5 mg/kg body weight) of enrofloxacin was administered intramuscularly (IM) to the healthy pigs. Using cannulation, the pharmacokinetic properties, including peak concentration (C max), time to reach C max (T max), and area under the curve (AUC), were determined in plasma and ileum content. The C max, T max, and AUC in the plasma were 1.09 ± 0.11 μg/mL, 1.27 ± 0.35 h, and 12.70 ± 2.72 μg·h/mL, respectively. While in ileum content, the C max, T max, and AUC were 7.07 ± 0.26 μg/mL, 5.54 ± 0.42 h, and 136.18 ± 12.50 μg·h/mL, respectively. Based on the minimum inhibitory concentration (MIC) data of 918 E. coli isolates, an E. coli O101/K99 strain (enrofloxacin MIC = 0.25 μg/mL) was selected for pharmacodynamic studies. The in vitro minimum bactericidal concentration (MBC), mutant prevention concentration (MPC), and ex vivo time-killing curves for enrofloxacin in ileum content were established against the selected E. coli O101/K99 strain. Integrating the in vivo pharmacokinetic data and ex vivo pharmacodynamic data, a sigmoid E max (Hill) equation was established to provide values for ileum content of AUC24h/MIC producing, bactericidal activity (52.65 h), and virtual eradication of bacteria (78.06 h). A dosage regimen of 1.96 mg/kg every 12 h for 3 days should be sufficient in the treatment of E. coli.
authors: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors: Jianyi
authors: J
authors: Wang
authors: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors: Haihong
authors: H
authors: Hao
authors: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University Wuhan, China.
authors: Lingli
authors: L
authors: Huang
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University Wuhan, China.
authors: Zhenli
authors: Z
authors: Liu
authors: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural UniversityWuhan, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural UniversityWuhan, China.
authors: Dongmei
authors: D
authors: Chen
authors: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural UniversityWuhan, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural UniversityWuhan, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Huazhong Agricultural UniversityWuhan, China.
authors: Zonghui
authors: Z
authors: Yuan
keywords: Escherichia coli; PK/PD modeling; enrofloxacin; pharmacodynamic; pharmacokinetic; pig