ceftiofur and Endotoxemia

The aim of this research was to compare plasma pharmacokinetics of ceftiofur sodium (CS) in healthy calves, and in calves with experimentally induced endotoxemia. Six calves received CS (2.2 mg/kg, IM) 2 hr after intravenous administration of 0.9% NaCl (Ceft group). After a washout period, the same 6 calves received CS 2 hr after intravenous injection of lipopolysaccharide (LPS+Ceft group). Another group of 6 calves received a combination of drug therapies that included CS 2 hr after administration of 0.9% NaCl (Comb group). A third group of 6 calves received the same combination therapy regimen 2 hr after intravenous injection of lipopolysaccharide (LPS+Comb group). Plasma concentrations of CS and all desfuroylceftiofur-related metabolites were determined using HPLC, and its pharmacokinetic properties were determined based on a two-compartment model. The peak concentration of CS in the LPS+Comb group occurred the earliest, and the clearance rate of CS was the highest in the Comb and LPS+Comb groups (P<0.05). The elimination half-life of CS in the LPS+Ceft group was longer than that in the Ceft and Comb groups (P<0.05). The results of this study indicate that combined therapies and endotoxemic status may alter the plasma pharmacokinetics of CS in calves.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Case-Control Studies; Cattle; Cattle Diseases; Cephalosporins; Drug Therapy, Combination; Endotoxemia; Injections, Intravenous; Lipopolysaccharides

The influence of ceftiofur on immune responses has been suggested by results of in vitro studies. This effect was studied using a murine model that measured mortality and early cytokine responses after challenge with endotoxin. To investigate the treatment of endotoxic mice with ceftiofur, mice were pretreated with ceftiofur at different times before and after challenge with a lethal dose of 30 mg/kg lipopolysaccharide (LPS). We found that 20 mg/kg ceftiofur had a significant protective effect and reduced the mortality of mice at early stages. To further understand the mechanism of action of ceftiofur, we examined plasma cytokine levels. Mice treated with LPS alone showed markedly increased plasma levels of TNF-alpha, IL-1beta, IL-6 and IL-10, whereas mice pretreated with 20 mg/kg ceftiofur showed significantly decreased plasma levels of TNF-alpha, IL-1beta and IL-6, but increased plasma levels of IL-10. These results support the idea that ceftiofur has a beneficial effect on LPS-induced endotoxemia caused by LPS through its modulation of cytokine levels. This confirms the effect of ceftiofur for the treatment of endotoxemia, which is caused by a Gram-negative bacterial infection.

Topics: Animals; Anti-Bacterial Agents; Cephalosporins; Cytokines; Disease Models, Animal; Endotoxemia; Female; Interleukin-10; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Time Factors; Tumor Necrosis Factor-alpha