In vivo pharmacokinetic/Pharmacodynamic modeling of Enrofloxacin against Escherichia coli in broiler chickens

BackgroundSystemic Escherichia coli infections cause early mortality of commercial broiler chickens. Although enrofloxacin has long been used in poultry, the in vivo pharmacokinetic/pharmacodynamic (PK/PD) relationship of enrofloxacin against E. coli is unclear. The present study aimed to establish an in vivo PK/PD model of enrofloxacin against E. coli in seven-day-old chicks and to ascertain whether the selection of target organ for PD determination is critical for parameter magnitude calculation in enrofloxacin PK/PD modeling.ResultsThe in vivo effectiveness of enrofloxacin against E. coli in different organs varied, with the E-max ranging from -4.4 to -5.8 Log(10) colony forming units (cfu)/mL or cfu/g. Both the surrogate AUC(0-24)/MIC of enrofloxacin or AUC(0-24)/MIC of the combination of enrofloxacin and ciprofloxacin correlated well with effectiveness in each organ. The AUC(0-24)/MIC ratio of the combination of enrofloxacin and ciprofloxacin producing bactericidal and elimination effects were 21.29 and 32.13 in blood; 41.68, and 58.52 in the liver; and 27.65 and 46.22 in the lung, respectively.ConclusionsThe in vivo effectiveness of enrofloxacin against E. coli in different organs was not identical after administration of the same dosage. To describe the magnitude of PK/PD parameter exactly, bacterial loading reduction in different organs as PD endpoints should be evaluated and compared in PK/PD modeling. The selection of a target organ to evaluate PDs is critical for rational dosage recommendation.