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Pharmacokinetic/pharmacodynamic relationship of marbofloxacin against Pasteurella multocida in a tissue-cage model in yellow cattle

Authors

  • Q. Shan,

    1. National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
    2. Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China
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  • J. Wang,

    1. National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
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  • F. Yang,

    1. National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
    2. College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China
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  • H. Ding,

    1. National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
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  • C. Liang,

    1. National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
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  • Z. Lv,

    1. National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
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  • Z. Li,

    1. National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
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  • Z. Zeng

    Corresponding author
    1. National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
    • Zhenling Zeng, National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. E-mail: zlzeng@scau.edu.cn

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  • Qi Shan, Jing Wang contributed equally to this work.

Abstract

The fluoroquinolone antimicrobial drug marbofloxacin was administered to yellow cattle intravenously and intramuscularly at a dose of 2 mg/kg of body weight in a two-period crossover study. The pharmacokinetic properties of marbofloxacin in serum, inflamed tissue-cage fluid (exudate), and noninflamed tissue-cage fluid (transudate) were studied by using a tissue-cage model. The in vitro and ex vivo activities of marbofloxacin in serum, exudate, and transudate against a pathogenic strain of Pasteurella multocida (Pmultocida) were determined. Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean values for the area under the curve (AUC)/MIC for serum, exudate, and transudate of 155.75, 153.00, and 138.88, respectively, after intravenous dosing and 160.50, 151.00, and 137.63, respectively, after intramuscular dosing. After intramuscular dosing, the maximum concentration/MIC ratios for serum, exudate, and transudate were 21.13, 9.13, and 8.38, respectively. The ex vivo growth inhibition data after intramuscular dosing were fitted to the inhibitory sigmoid Emax equation to provide the values of AUC/MIC required to produce bacteriostasis, bactericidal activity, and elimination of bacteria. The respective values for serum were 17.25, 31.29, and 109.62, and slightly lower values were obtained for transudate and exudate. It is proposed that these findings might be used with MIC50 or MIC90 data to provide a rational approach to the design of dosage schedules which optimize efficacy in respect of bacteriological as well as clinical cures.

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