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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  O 101 /K 99  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  O 101 /K 99  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 AUC 24h /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 .

Pharmacokinetic and Pharmacodynamic Integration and Modeling of Enrofloxacin in Swine for Escherichia coli