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An established LC-MS/MS method and a developed PK model for the study of pharmacokinetic properties of benapenem in infected mice 被引量:1
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作者 Xiwei Ji Zisheng Kang +4 位作者 Yun Li Xiping Yang Xifeng Ma Chongtie Shi Yuan Lv 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2019年第11期802-811,共10页
Benapenem is a new parenteral beta-lactam antibacterial with a broad antibacterial spectrum. In the present study, we developed and validated a simple, rapid and sensitive assay method using D6-benapenem as internal s... Benapenem is a new parenteral beta-lactam antibacterial with a broad antibacterial spectrum. In the present study, we developed and validated a simple, rapid and sensitive assay method using D6-benapenem as internal standard(IS) after one-step precipitation with methanol to determine benapenem in the plasma of infected mice. Separation was achieved on a reverse phase C18 column with a mobile phase composed of acetonitrile containing 0.2% formic acid–water(0.2% formic acid) and 10 mmol/L ammonium acetate in gradient elution mode. A triple quadrupole tandem mass spectrometer with electrospray ionization source was used as detector and operated by multiple reaction monitoring(MRM) in the positive ion mode. Calibration curves were linear(r>0.99) between 10 and 2000 ng/m L. The quantitative limit was 10 ng/m L, and the intra-and inter-precisions were <4.85% and <1.47%, respectively. The extraction recovery of benapenem and IS was 97.07%–107.09% and 92.47%–111.59%, respectively. The intra-and inter-accuracies were –9.70%– –11.00%, and the matrix effects of benapenem and IS were 85.68%–92.04% and 83.17%–92.04%, respectively. The method was successfully applied to the preclinical pharmacokinetic(PK) studies of benapenem. We also developed a two-compartment model to characterize the PK profiles of benapenem in infected mice, which could provide a better understanding of the PK properties of benapenem. 展开更多
关键词 LC-MS/MS benapenem Infected mice PHARMACOKINETICS Modeling
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新碳青霉烯类抗生素百纳培南的小鼠泌尿道感染药效学研究 被引量:2
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作者 卢曦 李聪然 +7 位作者 庞晶 胡辛欣 聂彤颖 杨信怡 李雪 李国庆 王秀坤 游雪甫 《中国医药生物技术》 2015年第2期139-143,共5页
目的评价新碳青霉烯类抗生素百纳培南对小鼠大肠埃希菌泌尿道上行性感染的体内疗效。方法通过泌尿道钝针头插管法,向小鼠膀胱内注入0.05 ml浓度为1010cfu/ml的大肠埃希菌9612菌液,建立小鼠泌尿道感染模型。于感染后6、24和30 h皮下给药... 目的评价新碳青霉烯类抗生素百纳培南对小鼠大肠埃希菌泌尿道上行性感染的体内疗效。方法通过泌尿道钝针头插管法,向小鼠膀胱内注入0.05 ml浓度为1010cfu/ml的大肠埃希菌9612菌液,建立小鼠泌尿道感染模型。于感染后6、24和30 h皮下给药,感染后48 h处死动物,取肾剖面盖印并研磨计数,对百纳培南进行体内药效学评价,并与对照药美罗培南、厄他培南进行比较。结果对大肠埃希菌9612泌尿道上行性感染小鼠,百纳培南8、2和0.5 mg/kg剂量组小鼠肾组织匀浆菌落计数明显低于对照组(P<0.01);8、2、0.5和0.125 mg/kg剂量组肾剖面盖印结果均与对照组有显著差异(P<0.01或P<0.05)。百纳培南与相同剂量美罗培南、厄他培南组相比,除0.125 mg/kg剂量组肾剖面盖印结果与厄他培南组有显著性差异(P<0.01)外,其他剂量组肾组织匀浆菌落计数和肾剖面盖印结果均无显著性差异(P>0.05)。结论对于小鼠泌尿道大肠埃希菌9612上行性感染,百纳培南可显著降低小鼠的肾组织菌落计数和肾剖面盖印阳性率,疗效与美罗培南、厄他培南相近。 展开更多
关键词 泌尿道感染 药效学评价 尿路致病性大肠埃希菌 百纳培南
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