The Study of Pharmacokinetics and Pharmacodynamics on Four Kinds of Bacteria of Cefbuperazone Sodium
|School||Hebei North University|
|Keywords||Cefbuperazone sodium β-Lactamase ESBLs Plasmaconcentration Minimum Inhibitory Concentration Serum BactericidalActivity Correlation FIC|
In recent years, bacterial drug resistance increased gravity with applied of P-lactam antibiotics widely. Extended Spectrum P-Lactamase (ESBLs) and Amp Cephalosporinase (AmpC enzyme) were the major reason of resistance.Cefbuperazone sodium is a new type antibiotics of cephamycin, belongs to the third generation. It is effective to many infections caused by sensitive bacteria.Cefbuperazone sodium inhibit Peptidoglycan synthesis of bacterial cell wssall as other cephalosporin. Cefbuperazone sodium has strong antibacterial activity to bacteria producing P-lactamase.1Cefbuperazone sodium pharmacokineticsDriping Cefbuperazone sodium in healthy subjects of Chinese through vein continuously. To determine blood concentration of Cefbuperazone sodium by HPLC. Twelve subjects single dose1g on first and eighth days, delivery1g on second to seventh days,q12h,100mL/h uniform intravenous infusion at1h. Drug-time curve with non-compartment model; The first time with the last time:Dose of Cmax were72.07±15.39μg/mL,76.97±13.21μg/mL; Dose of Tmax were1.035±0.043h,1.007±0.024h; Dose of t1/2were1.60±0.40h,1.53±0.16h. Compare the first and the last dose, main pharmacokinetic parameters were:Cmax、Tmax、t1/2. AUC0～t、Vz_obs、Vz、CL、CLss、Ke,the difference was not statistically significant (p>0.05); Comparison between women and men, main pharmacokinetic parameters of the difference was not statistically significant. Drug has not accumulated in the body after continuous administration.The pharmacokinetics parameters of Cefbuperazone sodium were similar with foreign documents reported.2Minimum inhibitory concentration of Cefbuperazone sodium on177strains of bacteria and study of PK/PDCefbuperazone sodium on producing ESBLs Escherichia coli, Klebsiella pneumoniae bacteria MIC50were1μg·ML-1and0.5μ g·ML-1,MIC9o was4μg·ML-1, sensitive rate was93～98%. Cefbuperazone sodium on MSSA MIC50and MIC90were16μg·ML-1, sensitive rates was90%. Sensitive and resistance rate in12kinds of medicine was better than that in other drugs except Carbapenems to producing ESBLs Escherichia coli, Klebsiella pneumoniae.3Serum Bactericidal Activity of Cefbuperazone sodiumDriping Cefbuperazone sodium in12healthy subjects through vein continuously,1g every time,at12hours interval, continuously7days. Collect subject serum after1h and12h following administration, centrifugate and cryopreservation. Determine SBS and SBA of Cefbuperazone sodium in vivo by microdilution. Serum Bactericidal Activity have shown very good results of Cefbuperazone sodium against producing ESBLs Escherichia coli, Klebsiella pneumonia but not so effective to MSSA. It can yield good results that Cefbuperazone sodium is used against serious infections caused by producing ESBLs Escherichia coli or Klebsiella pneumoniae.4Correlation of Blood drug level、MBC and SBACorrelation of Cefbuperazone sodium peak SBS and C/MIC were general. Correlation of Cefbuperazone sodium peak SBA and C/MBC was good. Good relevance of SBA and C/MBC provided the relevant basis for other antibiotics clinical research and application.5Combined drug sensitive test Cefbuperazone sodium combining with Ciprofloxacin and Amikacin in vitro respectively improved sensitive rate on producing ESBLs and AmpC strains and had a good antibacterial synergistic effect.It was a probable effective antibacterial drug combination and had a positive effect on infection caused by producing ESBLs and AmpC Enzyme strains in clinical therapeutic.