Distribution of marbofloxacin within the bronchoalveolar region of healthy          pigs

Ijiri, Moe; Ishikawa, Shingo; Jibiki, Yoshinori; Miyazawa, Masataka; Senokuchi, Akane; Hobo, Seiji

doi:10.1292/jvms.20-0239

Cited by 1 publication

(1 citation statement)

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“…BAL alters the composition of the epithelial lining fluid and cannot provide sampling at all necessary time points from single animals (20,21). Additionally, due to the uncertainty of the dilution factor between bronchoalveolar lavage fluid and the actual interstitial or epithelial lining fluid concentrations within the lungs, PK characteristics are often described based on total drug content rather than the free drug concentration (22)(23)(24). Microdialysis has been applied to measure the concentration of antimicrobial drugs in the fluid and provide preclinical drug development and clinical PK/PD data for antimicrobial drugs (25,26).…”

Section: Discussionmentioning

confidence: 99%

Lung microdialysis and in vivo PK/PD integration of cefquinome against Actinobacillus pleuropneumoniae in a porcine experimental lung infection model

Chen,

Li,

et al. 2024

Front. Vet. Sci.

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This study aim to explore the application of microdialysis in pharmacokinetic (PK) and pharmacodynamic (PD) integration of cefquinome against Actinobacillus pleuropneumoniae in a porcine experimental lung infection model. The model was established via intratracheal inoculation where average bacterial counts (CFU) in the lungs of infected pigs reached 6.57 log10 CFU/g after 3 h. The PK profiles of unbound cefquinome in lung dialysates were determined following intramuscular injection of single doses of 0.125, 0.25, 0.5, 1, 2, and 4 mg/kg. Lung dialysate samples were collected using microdialysis at a flow rate of 1.5 μL/min until 24 h. The PD studies were conducted over 24 h based on 10 intermittent dosing regimens and total daily doses ranged from 0.25 to 4 mg/kg and dosage intervals included 12 and 24 h. The lung tissue was collected after 24 h of treatment and homogenized for bacterial counts. The relationships between PK/PD parameters derived from lung dialysates and drug efficacy were analyzed using an inhibitory sigmoid Emax model. The percentage of time the free drug concentration exceeded the minimum inhibitory concentration (%fT > MIC) was the PK/PD index best describing the antimicrobial activity (R2 = 0.96) in the porcine experimental infection model. The %fT > MIC values required to achieve net bacterial stasis, 1, 2 and 3 log10 CFU/g reductions in the lung were 22.45, 28.86, 37.62, and 56.46%, respectively. Cefquinome exhibited time-dependent characteristics against A. pleuropneumoniae in vivo. These results provide valuable insights into the application of microdialysis in PK/PD integration model studies and optima regimen of cefquinome for the treatment of porcine respiratory diseases caused by A. pleuropneumoniae.

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