| As the large-scale application of third-generation cephalosporins in veterinary clinical,clinical bacteria has strong resistance due to the production of ESBLs enzymes, and the antibacterial activity of ceftiofur significantly reduced ,which was stronger animal exclusive antibiotics in small original amount . Tazobactam is a potent broad-spectrumβ- lactamase inhibitor, whose breadth of inhibitory activity spectrum and strength of inhibitory activity are superior to clavulanic acid and sulbactam, and whose inhibitory activity is better than sulbactam sodium on the common E. coli of clinical TEM genotypes ESBLs. In order to improve the antibacterial activity of ceftiofur and prolong the time of its antibacterial activity, Ceftiofur is often accompanied with tazobactam inhibitors as the compound composition applied in the veterinary clinic. In order to explore whether this preparation has the characteristic of increased-effect and long-lasting compared with the unilateral preparation and conventional preparation, the evaluation of efficacy and pharmacokinetics in rabbits of Ceftiofur Hydrochloride Injection was studied ,which provide a theoretical basis on this preparation's exploration and clinical application .In this study, the efficacy of compound preparation was evaluated in vivo or in vitro. We Selected TEM type of bacteria producing ESBLs by double disc synergy test and PCR amplification from Pathogenic E. coli isolated from clinical, and assayed antibacterial activity of compound or compound preparation of ceftiofur by tube dilution method in vitro. The results showed that for enzyme production strains, the MIC value of compound preparation of ceftiofur after adding tazobactam to 8:1-1:1 ratio, which enhanced antibacterial activity, was smaller than that of unilateral ceftiofur. Antibacterial activity of compound preparation to 8:1-1:1 ratio increased 1-16 times compared with monotherapy in vitro. Compound preparation overcome the resistance of clinical drug-resistant strains, which have good antibacterial activity and economical. Will Ceftiofur and tazobactam 8:1 ratio to prepare the compound compatible with the unilateral suspension preparation preparation, general preparations intramuscular injection were injected on the 3 day old chickens after artificial infection of enzyme (TEM) of E. coli in vivo. And we observed the mental state, appetite, and stool of the chicken after administration, then conducted pathological examination, calculated the rate of protection and relative weight of chickens. The results showed that the cure rate of compound preparation was 96.7% and relative weight gain was 88.0%, which were significantly higher than the unilateral group and the conventional preparation group. With 0.1～0.2mg / only, the 3 day old chickens after artificial infection of enzyme (TEM) of E. coli were injected intramuscularly. Once a day, using 3 days, it can reduce the loss of E. coli on chicken with good effects.High performance liquid chromatography was established to determine ceftiofur in plasma. Samples of plasma were extracted with methanol for protein deposition, and then centrifugal filtration. Chromatography was performed on a Diamonsil? C18 column with a mobile phase consisting of acetonitrile-water-phosphate(V:V:V=28:72:0.1),delivered at 1 m L·min-1 , the detection wavelength was at 292 nm and the injection volume was 20μL. At last the concentration was calculated by external standard method. The method was simple,accurat and high precision for the content determination of ceftiofur, the average recoveries was 86.73%, the intra-day and inter-day coefficient of variation were 2.01～6.0%,3.24～7.49%. The calibration curvewas linear in the range of 0.18μg/mL～52.9μg/mL(r=0.9992).In this study, ceftiofur suspension compound (CSC) in rabbits pharmacokinetics were studied. After intramuscular injection of CSC, simple recipe and conventional preparation (ceftiofur powder for injection) in rabbits, the blood concentration of drugs were determined at the different time points and to study drug in vivo metabolism characteristics. The results showed that the CSC in vivo pharmacokinetics are two-compartment open model. The main pharmacokinetic parameters are as flowing: the distribution phase half-life (T1/2a) for 0.765h, the elimination phase half-life (T1/2β) for 19.762h, the area under the concentration-time curve (AUC) for 294.76mg / L * h, the peak time (Tmax) for 2h, the peak concentration (Cmax) for 19.18mg / L, the mean residence time (MRT) for 20.24h. conventional preparation (ceftiofur powder for injection) compared, suspension formulations prolonged significantly the drug's elimination half-life, maintained an effective blood concentration in vivo long time. By comparing the simple recipe suspension of ceftiofur, two formulations of the metabolic processes in the body were similar to tazobactam have no significant impact on ceftiofur pharmacokinetics in vivo behavior.Both in the composition of compound have pharmacokinetic theoretical feasibility.
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