Murine Thigh Microdialysis to Evaluate the Pharmacokinetic/Pharmacodynamic Integration of Cefquinome Against Actinobacillus pleuropneumoniae

Abstract

This study aimed to explore the application of microdialysis in pharmacokinetic (PK)/pharmacodynamic (PD) integration of cefquinome against <i>Actinobacillus pleuropneumoniae</i>. After the <i>A. pleuropneumoniae</i> population reached 10⁶ CFU/thigh, the mice received 0.04, 0.16, 0.63, 2.5, and 10 mg/kg cefquinome by subcutaneous injection. Plasma samples were collected by retro-orbital puncture for 4 h, and thigh dialysate was obtained by microdialysis at a flow rate of 1.5 μL/min for 6 h for the PK study. For the PD experiment, the infected mice were treated with a 4-fold-increase in the total cefquinome dose, ranging from 0.01 to 10 mg/kg/24 h, divided into one, two, three, four, and eight doses. The number of bacteria was determined and an inhibitory sigmoid maximum effect (E_max) model was used to analyse the relationships between PK/PD parameters and efficacy. The mean penetration of cefquinome from plasma to the thigh was 0.591. The PK data for PK/PD integration were obtained by extrapolation. The fittest PK/PD parameter for efficacy evaluation was %<i>f</i>T>MIC (the percentage of time that free drug concentrations exceed the MIC). The magnitudes of %<i>f</i>T>MIC to achieve net bacterial stasis, 1-log₁₀ CFU reduction, 2-log₁₀ CFU reduction, and 3-log₁₀ CFU reduction were 19.56, 28.65, 41.59, and 67.07 % in plasma and 21.74, 36.11, 52.96, and 82.68% in murine thigh, respectively. Microdialysis was first applied to evaluate the PK/PD integration of cefquinome against <i>A. pleuropneumoniae</i>. These results would provide valuable references when we apply microdialysis to study the PK/PD integration model and use cefquinome to treat animal diseases caused by <i>A. pleuropneumoniae</i>.