Effect of supportive therapy on the pharmacokinetics of intravenous marbofloxacin in endotoxemic sheep

摘要: The purpose of this study was to determine the influences supportive therapy (ST) on pharmacokinetics (PK) marbofloxacin in lipopolysaccharide (LPS)-induced endotoxemic sheep. Furthermore, minimum inhibitory concentration (MIC) against Escherichia coli, Mannheimia haemolytica, Pasteurella multocida, Klebsiella pneumoniae, Salmonella spp., and Staphylococcus aureus determined. performed using a three-period cross PK design following 15-day washout period. In first period, (10 mg/kg) administered by an intravenous (IV) injection. second third periods, co-administered with ST (lactated ringer + 5% dextrose + 0.45% sodium chloride, IV, 20 ml/kg, dexamethasone 0.5 mg/kg, SC) ST + LPS (E. coli O55:B5, 10 µg/kg), respectively. Plasma measured HPLC-UV. Following IV administration alone, t1/2λz , AUC0-∞ ClT Vdss were 2.87 hr, 34.73 hr × µg/ml, 0.29 L hr-1  kg-1 0.87 L/kg, While no change found MBX + ST group terms parameters marbofloxacin, it determined that decreased, increased, MRT prolonged MBX + ST + LPS group. MIC values 0.031 >16 µg/ml for E. coli, 0.016 M. haemolytica, 0.016-1 µg/ml P. multocida, 0.016-0.25 µg/ml K. pneumoniae, 0.031-0.063 µg/ml 0.031-1 µg/ml S. aureus. results show necessity make dose adjustment concomitant Also, pharmacodynamic effect needs be naturally infected septicemic sheep single ST.