| Panipenem(PAPM)/ betamipron(BP) is a newly developed carbapenem antibiotic agent,in which PAPM was mixed with BP in a ratio of l:l(wt/wt). The studies had verified that PAPM had a broad antibacterial spectrum against gram-positive and gram-negative bacteria and was stable to the hydrolysis of various types of beta-lactamase. And BP which derived from amino-acid effected as a renal anion-transport inhibitor for the purpose of reducing the renal toxicity of PAPM by inhibiting PAPM into renal cortex cells through competitive with PAPM in membrane transport.In the recent years, some gram-negative organisms caused nosocomial infections such as Klebsiella pneumoniae and Enterobacter cloacae often showed a lower sensibilities to the second and third generation of cephalosporins, but most of them were still susceptible to the carbapenem antibiotics. Even so, since the bacterial susceptibility and the drug plasma concentration were two major factors that influenced therapeutic effect of antibiotics, and the dose and the time of antibiotic administration would directly affect the drug plasma concentration, it is important to understand that both the sensibility of clinical isolates to PAPM/BP and the pharmacokinetics in the Chinese patients before prescribing this drug in clinical practice.In this study the antimicrobial activity of PAPM/BP in vitro was evaluated and its pharmacokinetic in patients with respiratory tract infections was investigated. The main objective of our study was to provide experimental basis for the reasonable administration of PAPM/BP in China.Method:1. The study of in vitro antimicrobial activity of PAPM/BPThe minimal inhibition concentrations (MICs) of PAPM/BP to 247 clinical isolates were determined by agar dilution method. And the susceptibility to the bacteria of PAPM/BP was in comparision to that of imipenem, meropenem, ceftazidime, sulbactam sodium/ cefoperazone and oxacillin. In addition the minimal bactericidal concentrations(MBCs) of PAPM/BP to some clinical isolates were determined.2. The study of pharmacokinetics of PAPM/BP in patients with respiratoy tract infectionsSamples from plasma and urine of patients administrated PAPM/BP were collected and added with Imol/L MOPS [3-(N- morpholino)propanesulfonic acid;pH7.0] in a ratio of 1:1 and 1:2 (V/V) immediately, respectively, and stored at -65 癈 for HPLC analysis.PAPM/BP in the samples were quantitatively analyzed by HPLC methods reported by Hisaoka et al. The analysis of BP were by HPLC with internal standard of N-benzoyl- DL-alanine, while PAPM was examined without the internal standard. HPLC conditions for PAPM were as follows: a chromatogram column of Cjg Diamosil (TM) was 250x4.6mm, Sum. Mobile phases were CH3OH: CHsCOONR, (0.04mol/L, pH4.0)/5:95 in plasma and CH3OH: CH3COONH4 (0.04 mol/L, pH4.0)/2:98 in urine. And the flow rate was 1.6ml/min. They were determined at UV wavelength of 299.3 nm. The conditions for BP: the column was the same as described before. Mobile phases were CH3CN:CH3COOH:H2O/20:1:79 and CH3CN: CH3COOH: H2O/ 12:1:87, and the flow rate were 1.4ml/min and 1.6ml/min in plasma and urine, respectively. The absorption spectra of UV were detected at wavelength of 240nm.Result:1. in vitro antimicrobial activity of PAPM/BPin1.1 In vitro antimicrobial activity of PAPM/BP was almost the same as that of PAPM, The results indicated that antimicrobial activity was due to PAPM.1.2 PAPM/BP had a strong antimicrobial activity against Staphylococcus aureus including Methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, 3 -Streptococcus hemolytic, Streptococcus pneumoniae, Micrococcus, Staphylococcus pneumoniae, Escherichia coli and Klebsiella pneumoniae. MIC5o and MIC90 to these bacteria strains were about =$0.0075 mg/L and <0.0075~2 mg/L, respectively. The drug had also showed a potent effect against Haemophilus influenzae (MIC O.0075 ~0.125mg/L), Enterobacter cloacae (MICso 0.125mg/L), Proteus (MICso... |
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