Pharmacokinetic/pharmacodynamic relationship of marbofloxacin against Pasteurella multocida in a tissue-cage model in yellow cattle.
Pharmacokinetic/pharmacodynamic relationship of marbofloxacin against Pasteurella multocida in a tissue-cage model in yellow cattle.
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DOI：
10.1111/jvp.12078
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发表时间：
2014-06
影响因子：
1.3
通讯作者：
Qi Shan;Qi Shan;J. Wang;Fan Yang;Fan Yang;H. Ding;C. Liang;Z. Lv;Z. Li;Z. Zeng
中科院分区：
文献类型：
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作者：
Qi Shan;Qi Shan;J. Wang;Fan Yang;Fan Yang;H. Ding;C. Liang;Z. Lv;Z. Li;Z. Zeng
在一项两阶段交叉研究中，以2 mg/kg体重的剂量静脉和肌肉注射给予黄牛氟喹诺酮类抗菌药物马波沙星。采用组织笼模型研究了马波沙星在血清、炎症组织笼液（渗出液）和非炎症组织笼液（漏出液）中的药代动力学特性。测定了马波沙星在血清、渗出液和漏出液中对多杀性巴氏杆菌致病菌株的体外和离体活性。将体内药代动力学数据与体外MIC整合后，静脉给药后血清、渗出液和漏出液的曲线下面积（AUC）/MIC平均值分别为155.75、153.00和138.88，肌内给药后分别为160.50、151.00和137.63。肌内给药后，血清、渗出液和漏出液的最大浓度/MIC比值分别为21.13、9.13和8.38。将肌内给药后的离体生长抑制数据拟合至抑制性S形Emax方程，以提供产生抑菌、杀菌活性和消除细菌所需的AUC/MIC值。血清的相应值分别为17.25、31.29和109.62，漏出液和渗出液的值略低。建议将这些发现与MIC 50或MIC 90数据一起使用，以提供一种合理的方法来设计剂量方案，从而优化细菌学和临床治愈方面的疗效。
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 (P. multocida) 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.