甲磺酸帕珠沙星注射液临床药代动力学/药效学研究  

Clinical Pharmacokinetics/Pharmacodynamics Study on Pazufloxacin Methanesulphonate Injection

作　　者：王宪刚[1] 苗佳[1] 梁德荣[1] 余勤[1] 梁茂植[1] 张淑华[2] 

机构地区：[1]四川大学华西医院临床药理研究所,成都610041 [2]四川抗菌素工业研究所

出　　处：《四川大学学报（医学版）》2009年第4期689-693,共5页Journal of Sichuan University(Medical Sciences)

摘　　要：目的通过比较300mg和500mg甲磺酸帕珠沙星注射液临床药代动力学/药效学(PK/PD)参数,指导临床合理应用抗菌药物。方法对24例健康受试者分别进行300mg与500mg帕珠沙星单次和多次给药的药代动力学研究,采用反相高效液相色谱-紫外检测法(RPHPLC-UV)测定血浆中帕珠沙星浓度;采用二倍琼脂稀释法检测帕珠沙星对7种130株临床常见致病菌的最低抑菌浓度(MIC)及5种90株菌的防突变浓度(MPC),计算PK/PD参数。结果当血药浓度达稳态后,甲磺酸帕珠沙星300mg与500mg每12h(Q12h)静滴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分别为215.36与309.60和107.68与154.80,Cmax/MIC50分别是57.52与81.28和28.76与40.64;但对耐甲氧西林金黄色葡萄球菌(MRSA)的AUC0-24/MIC均远小于40。其对铜绿假单胞菌的AUC0-24/MIC50和Cmax/MIC50均分别大于100和10;而对大肠埃希菌,肺炎克雷伯菌和鲍曼不动杆菌的AUC0-24/MIC50均远小于100,Cmax/MIC50小于或接近10。仅甲磺酸帕珠沙星500mgQ12h静滴对MSSA具有较强的防突变能力,300mg和500mgQ12h静滴对其它致病菌均无防突变能力。结论甲磺酸帕珠沙星300mg和500mgQ12h静滴治疗急性细菌性感染疗效相当,故推荐临床用药方案为300mgQ12h静滴。Objective To identify rational dosage regimen for pazufloxacin methanesulphonate injection through a pharmacokinetics/pharmacodynamics （PK/PD） study. Methods Pazufloxacin methanesulphonate at the doses of 300mg 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 rag, respectively. The Cmax/MIC50 were 57.52 and 28.76 at the dose of 300 rag, 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 500mg, but not for other pathogenic bacteria either at 300 mg or 500 rag. 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.

关 键 词：帕珠沙星 PK/PD MIC MPC RPHPLC-UV 

分 类 号：R96[医药卫生—药理学]