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This study was aimed at applying microdialysis to explore cefquinome pharmacokinetics in thigh and plasma of healthy, neutropenic, and  Actinobacillus pleuropneumoniae -infected mice. The relative recoveries (RRs) were tested  in vitro  by dialysis and retrodialysis and  in vivo  by retrodialysis. ICR mice were randomly divided into four groups: H-40 (healthy mice receiving cefquinome at 40 mg/kg), H-160, N-40 (neutropenic mice), and I-40 mg/kg (thigh infected-mice with  A. pleuropneumoniae ). After cefquinome administration, plasma was collected by retro-orbital puncture and thigh dialysate was collected by using a microdialysis probe with Ringer’s solution at a perfusion rate of 1.5 μL/min. Plasma and thigh dialysate samples were assessed by HPLC–MS/MS and analyzed by a non-compartment model. The mean  in vivo  recoveries in the thigh were 39.35, 38.59, and 37.29% for healthy, neutropenic, and infected mice, respectively. The mean plasma protein-binding level was 16.40% and was independent of drug concentrations. For all groups, the mean values of the free AUC inf  in plasma were higher than those in murine thigh, while the elimination  T  1/2β  for plasma were lower than those for murine thigh. Cefquinome penetration (AUC thigh /AUC plasma ) from the plasma to thigh was 0.76, 0.88, 0.47, and 0.98 for H-40, N-40, I-40, and H-160 mg/kg, respectively. These results indicated that infection significantly affected cefquinome pharmacokinetics in murine thigh. In conclusion, we successfully applied a microdialysis method to evaluate the pharmacokinetics of cefquinome in murine thigh of healthy, neutropenic, and  A. pleuropneumonia -infected mice and the pharmacokinetics of cefquinome was obviously affected by infection in thigh.

frontiers in pharmacology

Microdialysis Determination of Cefquinome Pharmacokinetics in Murine Thigh From Healthy, Neutropenic, and Actinobacillus pleuropneumoniae-Infected Mice