Journal
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
Volume 41, Issue 6, Pages 887-893Publisher
WILEY
DOI: 10.1111/jvp.12678
Keywords
A. hydrophila; crucian carp; enrofloxacin; pharmacokinetic/pharmacodynamics model; pharmacokinetics
Categories
Funding
- National Natural Science Foundation of China [31502125]
- Major Science and Technology Projects of Guangdong province [2017B020231001]
- National Agricultural Product Quality Safety Risk Assessment Project [GJFP201700902]
- Project of Science and Technology of Guangdong Province [2017B030314171]
- Natural Science Foundation of Guangdong Province [2015A030310086]
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The pharmacokinetic (PK) properties of enrofloxacin (ENR) and its metabolite ciprofloxacin (CIP) were investigated in crucian carp following oral administration at different dose levels (5, 10, 20, 40 mg/kg body weight). The disposition kinetics of ENR was found to be linear over the dose range studied. Serum half-lives ranged from 64.56 to 72.68 hr. The in vitro and ex vivo activities of ENR in serum against a pathogenic strain of Aeromonas hydrophila were determined. In vitro and ex vivo bactericidal activity of ENR was concentration dependent. Dosing of 10 mg/kg resulted in an AUC/minimum inhibitory concentration (MIC) ratio of 368.92 hr and a C-max/MIC ratio of 7.23, respectively, against A. hydrophila 147 (MIC = 0.48 mu g/ml), indicating a likely high level of effectiveness in clinical infections caused by A. hydrophila with MIC value <= 0.48 mu g/ml. Modeling of ex vivo growth inhibition data to the sigmoid Emax equation provided the values of AUC(24 hr)/MIC required to produce bacteriostasis, bactericidal activity, and elimination of bacteria, these values were 21.70, 53.01, and 125.21 hr, respectively. These findings in conjunction with MIC90 data suggested that ENR at the dose of 7.81 mg/kg predicted a positive clinical outcome and minimize the risk of emergence of resistance.
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