摘要
目的:研究健康受试者口服氟罗沙星的药动学(PK)和药效学(PD),从而优化氟罗沙星的临床给药方案。方法:采用三周期自身交叉对照的方式对15名健康受试者分别口服200,300,400 mg氟罗沙星片后,以高效液相色谱法(HPLC)测定血药浓度,进而求出药动学(PK)参数。体外药效学(PD)研究是测定氟罗沙星对临床分离的15种494株常见致病菌的最低抑菌浓度(MIC)。以AUC0-24/MIC作为氟罗沙星的PK/PD参数(靶值为100和125),采用蒙特卡洛(Monte Carlo)模拟评价氟罗沙星的3种治疗方案对不同分离菌株AUC0-24/MIC值的药效学累积反应分数(CFR)。结果:以CFR>90%作为抗感染经验治疗的合理选择,对于大肠杆菌和淋球菌引起的感染,或口服200 mg(qd)即可;对硝酸盐阴性杆菌、肠杆菌属和哈夫尼亚菌属引起的感染,或口服300 mg(qd)即可;对于表葡球菌、铜绿假单胞菌、志贺菌属、肺炎克雷伯杆菌、柠檬酸杆菌属、普通变形杆菌、肺炎链球菌、沙门菌属和金葡球菌(MSSA)引起的感染,或口服400 mg(qd)可获得预期满意的临床疗效并能有效预防细菌耐药性产生,而对于耐甲氧西林金葡菌(MRSA),PK/PD参数显示疗效不佳。结论:应用Monte Carlo模拟评价氟罗沙星的PK/PD参数,可以为氟罗沙星的临床最佳给药方案的制定提供参考依据。
OBJECTIVE To investigate pharmacokinetics（PK）and pharmacodynamics（PD）of oral fleroxacin tablets in healthy Chinese volunteers and to provide evidences for optimal clinical dosing regimen.METHODS The serum drug concentrations were assayed by HPLC method and pharmacokinetic parameters were calculated after intravenous infusion of 200,300 mg and 400 mg fleroxacin at single dose to 15 healthy volunteers by a three period self cross-over clinical trial.Minimal inhibitory concentrations（MIC）of leroxacin against 494 clinical isolates of 15 strains were determined.Based on the above results,PK/PD parameter AUC0-24/MIC was calculated.The cumulative fraction of responses（CFR）of fleroxacin on AUC0-24/MIC values of different isolates were evaluated using Monte Carlo simulation.RESULTS With CFR90% as the optimal dosage regimen of empirical therapy,the lowest oral dose was 200 mg（qd）for infection of Escherichia coli and Neisseria gonorrhoeae,300 mg（qd）for nitrate-negative bacillus,enterobacter and Enterobacter hafniae,and 400 mg（qd）for surface staphylococcus aureus,Pseudomonas aeruginosa,Shigella,Klebsiella pneumoniae,Citrobacter,Proteus,Streptococcus pneumoniae,Salmonella and Staphylococcus aureus（MSSA）,to acquire satisfactory clinical efficacy and effectively prevent drug resistance.CONCLUSION PK/PD parameters of fleroxacin evaluated by Monte Carlo simulation can help to develop clinical optimal dosing regimen for fleroxacin.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2015年第9期790-794,共5页
Chinese Journal of Hospital Pharmacy
基金
河南省科技攻关项目(编号:092102310275)
