[Clinical pharmacokinetics/pharmacodynamics study on pazufloxacin methanesulphonate injection].
[Clinical pharmacokinetics/pharmacodynamics study on pazufloxacin methanesulphonate injection].
复制标题
甲磺酸帕珠沙星注射液临床药动学/药效学研究
DOI：
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
Shu
中科院分区：
文献类型：
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作者：
Xianghui Wang;J. Miao;De;Qin Yu;M. Liang;Shu
目标
通过药代动力学/药效学（PK/PD）研究确定甲磺酸帕珠沙星注射液的合理给药方案。
方法
给 24 名健康志愿者注射 300 mg 和 500 mg 剂量的甲磺酸帕珠沙星。通过RPHPLC-UV测定帕珠沙星的血浆浓度。采用双肉汤稀释法测定了帕珠沙星对7种细菌130株的MIC，以及帕珠沙星对5种细菌的MPC。
结果
甲磺酸帕珠沙星在稳定浓度状态下对甲氧西林敏感金黄色葡萄球菌(MSSA)和肺炎链球菌的AUC0-24/MIC50在300mg剂量时分别为215.36和107.68，在500mg剂量时分别为309.60和154.80。 300mg剂量下的Cmax/MIC50分别为57.52和28.76，500mg剂量下的Cmax/MIC50分别为81.28和40.64。然而，甲磺酸帕珠沙星对耐甲氧西林金黄色葡萄球菌（MRSA）的AUC0-24/MIC远小于40。300 mg和500 mg剂量的帕珠沙星对铜绿假单胞菌的AUC0-24/MIC50和Cmax/MIC50均超过定义的标准100和10。帕珠沙星对大肠杆菌、肺炎克雷伯菌和鲍曼不动杆菌的AUC0-24/MIC和Cmax/MIC远小于100和10。甲磺酸帕珠沙星在500 mg剂量下防止MSSA突变的能力很强，但在300 mg和500 mg剂量下对其他病原菌的抑制能力较差。
结论
300 mg 和 500 mg 剂量的甲磺酸帕珠沙星在治疗急性细菌感染方面具有相似的功效。推荐剂量方案为300 mg Q12h静脉滴注。
OBJECTIVE
To identify rational dosage regimen for pazufloxacin methanesulphonate injection through a pharmacokinetics/pharmacodynamics (PK/PD) study.
METHODS
Pazufloxacin methanesulphonate at the doses of 300 mg and 500 mg were injected to 24 healthy volunteers. The plasma concentrations of pazufloxacin were measured by RPHPLC-UV. The MICs of pazufloxacin against 130 strains of 7 species of bacterias, as well as the MPCs of pazufloxacin against 5 species of bacterias were measured by double broth dilution method.
RESULTS
The AUC0-24/MIC50 of pazufloxacin methanesulphonate at a stabilized concentration state against methicillin-sensitive Staphylococcus aureus (MSSA) and S. pneumoniae were 215.36 and 107.68 at the dose of 300 mg, and 309.60 and 154.80 at the dose of 500 mg, respectively. The Cmax/MIC50 were 57.52 and 28.76 at the dose of 300 mg, and 81.28 and 40.64 at the dose of 500 mg, respectively. However, the AUC0-24/MIC of pazufloxacin methanesulphonate against methicillin-resistant staphylococcus aureus (MRSA) were far less than 40. Both the AUC0-24/MIC50 and the Cmax/MIC50 of pazufloxacin against P. aeruginosa at the doses of 300 mg and 500 mg exceeded the defined criteria 100 and 10. Whereas the AUC0-24/MIC and Cmax/MIC of pazufloxacin against E. coli, K. pneumoniae and A. baumanii were much less than 100 and 10. The capability of pazufloxacin methanesulphonate to prevent mutations of MSSA was strong at the dose of 500 mg, but not for other pathogenic bacteria either at 300 mg or 500 mg.
CONCLUSION
Pazufloxacin methanesulphonate at the dose of 300 mg and 500 mg have similar efficacy in treating acute bacterial infections. The dosage regimen of 300 mg Q12h intravenous infusion is recommended.