The purpose of this study was to determine the influences of supportive therapy (ST) on the pharmacokinetics (PK) of marbofloxacin in lipopolysaccharide (LPS)-induced endotoxemic sheep. Furthermore, minimum inhibitory concentration (MIC) of marbofloxacin against Escherichia coli, Mannheimia haemolytica, Pasteurella multocida, Klebsiella pneumoniae, Salmonella spp., and Staphylococcus aureus was determined. The study was performed using a three-period cross PK design following a 15-day washout period. In the first period, marbofloxacin (10 mg/kg) was administered by an intravenous (IV) injection. In the second and third periods, marbofloxacin was co-administered with ST (lactated ringer + 5% dextrose + 0.45% sodium chloride, IV, 20 ml/kg, dexamethasone 0.5 mg/kg, SC) and ST + LPS (E. coli O55:B5, 10 µg/kg), respectively. Plasma marbofloxacin concentration was measured using HPLC-UV. Following IV administration of marbofloxacin alone, the t 1 / 2 λ z , AUC0-∞ , ClT , and Vdss were 2.87 hr, 34.73 hr × µg/ml, 0.29 L hr-1 kg-1 , and 0.87 L/kg, respectively. While no change was found in the MBX + ST group in terms of the PK parameters of marbofloxacin, it was determined that the ClT of marbofloxacin decreased, AUC0-∞ increased, and t 1 / 2 λ z and MRT prolonged in the MBX + ST + LPS group. MIC values of marbofloxacin were 0.031 to >16 µg/ml for E. coli, 0.016 to >16 µg/ml for M. haemolytica, 0.016-1 µg/ml for P. multocida, 0.016-0.25 µg/ml for K. pneumoniae, 0.031-0.063 µg/ml for Salmonella spp., and 0.031-1 µg/ml for S. aureus. The study results show the necessity to make a dose adjustment of marbofloxacin following concomitant administration of ST in endotoxemic sheep. Also, the PK and pharmacodynamic effect of marbofloxacin needs to be determined in naturally infected septicemic sheep following concomitant administration of single and ST.

中文翻译：

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支持疗法对内毒素血症绵羊静脉注射马波沙星药代动力学的影响。

这项研究的目的是确定支持疗法（ST）对脂多糖（LPS）诱导的内毒素血症绵羊中马波沙星的药代动力学（PK）的影响。此外，测定了马尔福沙星对大肠杆菌，溶血曼海姆氏菌，多杀性巴斯德氏菌，肺炎克雷伯菌，沙门氏菌和金黄色葡萄球菌的最小抑制浓度（MIC）。在15天的清除期后，使用三期交叉PK设计进行了研究。在第一个阶段，通过静脉注射（IV）注射marbofloxacin（10 mg / kg）。在第二期和第三期中，将马波沙星与ST（乳酸林格氏液+ 5％葡萄糖+ 0.45％氯化钠，静脉注射，20 ml / kg，地塞米松0.5 mg / kg，SC）和ST + LPS（大肠杆菌）联合给药O55：B5，分别为10 µg / kg）。使用HPLC-UV测量血浆马波沙星浓度。单独静脉注射marbofloxacin后，t 1/2λz，AUC0-∞，ClT和Vdss分别为2.87小时，34.73小时×µg / ml，0.29 L hr-1 kg-1和0.87 L / kg。 。虽然在MBX + ST组中未发现根据马波沙星的PK参数发生变化，但可以确定，MBX + ST中马波沙星的ClT降低，AUC0-∞升高，t 1/2λz和MRT延长。 + LPS组。大肠杆菌的marbofloxacin MIC值为0.031至> 16 µg / ml，溶血支原体为0.016至> 16 µg / ml，多杀毕赤酵母为0.016-1 µg / ml，肺炎克雷伯菌为0.016-0.25 µg / ml沙门氏菌为0.031-0.063 µg / ml，金黄色葡萄球菌为0.031-1 µg / ml。研究结果表明，在内毒素血症的绵羊中同时服用ST后，有必要调整马尔波沙星的剂量。同样，在单剂和ST联合给药后，需要确定自然感染的败血性绵羊中马波沙星的PK和药效学作用。