Shan Q, Wang J, Yang F, Ding H, Liang C, Lv Z, Li Z, Zeng Z
National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China.
J Vet Pharmacol Ther. 2014 Jun;37(3):222-30. doi: 10.1111/jvp.12078. Epub 2013 Aug 26.
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.
在一项两阶段交叉研究中，给黄牛静脉注射和肌肉注射氟喹诺酮类抗菌药物马波沙星，剂量为2毫克/千克体重。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巴斯德氏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最低抑菌浓度（MIC）相结合，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，肌肉给药后分别为160.50、151.00和137.63。肌肉给药后，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。将肌肉给药后的离体生长抑制数据拟合到抑制性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。建议这些研究结果可与MIC50或MIC90数据一起使用，为设计优化细菌学和临床治愈疗效的给药方案提供合理方法。
