AUTHOR=Zhang Longfei , Yao Lihua , Kang Zheng , Huang Zilong , Gu Xiaoyan , Shen Xiangguang , Ding Huanzhong 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00249

DOI=10.3389/fphar.2019.00249

ISSN=1663-9812

ABSTRACT=<p>This study was aimed at applying microdialysis to explore cefquinome pharmacokinetics in thigh and plasma of healthy, neutropenic, and <italic>Actinobacillus pleuropneumoniae</italic>-infected mice. The relative recoveries (RRs) were tested <italic>in vitro</italic> by dialysis and retrodialysis and <italic>in vivo</italic> 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 <italic>A. pleuropneumoniae</italic>). 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 <italic>in vivo</italic> 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<sub>inf</sub> in plasma were higher than those in murine thigh, while the elimination <italic>T</italic><sub>1/2β</sub> for plasma were lower than those for murine thigh. Cefquinome penetration (AUC<sub>thigh</sub>/AUC<sub>plasma</sub>) 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 <italic>A. pleuropneumonia</italic>-infected mice and the pharmacokinetics of cefquinome was obviously affected by infection in thigh.</p>