中国健康受试者左氧氟沙星片单剂及多剂药代动力学研究  

Single-dose and multiple-dose pharmacokinetics of levofloxacin in Chinese healthy subjects

作　　者：郁继诚[1] 张菁[1] 曹国英[1] 郭蓓宁[1] 武晓捷[1] 施耀国[1] 张婴元[1] 

机构地区：[1]复旦大学附属华山医院抗生素研究所,卫生部抗生素临床药理重点实验室,上海200040

出　　处：《第三军医大学学报》2013年第23期2516-2520,共5页Journal of Third Military Medical University

基　　金：国家科技重大新药创制专项资助(2012ZX09303004-001)~~

摘　　要：目的研究中国健康志愿者口服左氧氟沙星片单剂及多剂给药的药代动力学特征。方法①单剂给药组：单剂空腹口服200、500mg或700mg左氧氟沙星片，每剂量组9例受试者；②多剂给药组：9例受试者接受左氧氟沙星500mg，每天1次，连续7d多剂给药。采用高效液相色谱法测定血、尿样本中左氧氟沙星浓度。结果①受试者单剂空腹口服左氧氟沙星片200、500、700mg后血药峰浓度（Cmax）分别为（2.43±0.63）、（7.03±2.47）、（8.96±1.95）mg／L，药时曲线下面积（AUC0-∞）分别为（17.07.4±1.52）、（54.76±8.74）、（85.54±9.12）mg·h／L，消除半衰期（T1/2）均大于7h，给药后72h内累积尿排出率大于80％。②多次给药第7天与初次给药第1天的Cmax、C24h、AUC0～24h。的比分别为1.0415、1.0314、1.1263、经过7d的反复给药，与吸收分布有关的参数并不增大，显示体内无蓄积性。给药第7天给药后24h为止的累积尿中排泄率为86.56％。③左氧氟沙星500mg每天1次给药方案对肺炎链球菌等能达到药动学／药效学（PK／PD）靶值。结论受试者口服左氧氟沙星片后吸收迅速，主要经肾脏消除。多剂给药后无蓄积。不良反应轻微、受试者均能耐受。PK／PD结果提示左氧氟沙星片500mg每天1次给药方案用于由肺炎链球菌等引起的下呼吸道感染，预期可获得良好的临床和微生物疗效。Objective To investigate the pharmacokinetics of levofloxacin in Chinese healthy subjects after single and multiple oral doses of levofloxacin for guiding rational clinical regimen in patients with infectious diseases. Methods The drug concentrations in the plasma and urine were assayed by high performance liquid chromatography （HPLC） and the pharmacokinetie parameters were calculated after a single oral dose of 200, 500 or 700 mg levofloxacin to 9 healthy subjects for each dose group, and after multiple doses of 500 mg daily for 7 consecutive days in 9 subjects. Results After single dose administration of 200, 500 and 700 mg levofloxacin, the peak concentration （Cmax） of levofloxacin in the plasma were 2.43±0.63, 7.03±2.47 and 8.96±1.95 mg/L respectively, the area under the concentration-time curve （AUC0-∞） were 17.07±1.52, 54.76±8.74 and 85.54±9.12 mg·h/L respectively, the values of T1/2β were all longer than 7 h, and the doses being excreted in the urine within 72 h for each dose group accounted for over 80%. After multiple doses of levofloxacin administration to the subjects, the values of Cmax C24h, AUC0-24h ratio of day 7 over day 1 was 1.041 5, 1.031 4 and 1.126 3 respectively. The parameters related to drug absorption and distribution did not show obvious increase after 7 days＇ multiple dose administration to all the subjects. No accumulation was observed after multiple doses administration. About 85.65 % of the doses were excreted in the urine within 24 h in day 7. The regimen of 500 mg levofloxacin once daily reached the pharmacokinetic/pharmacodynamic （PK/PD） target for Streptococcus pneumoniae. Conclusion Levofloxacin is absorbed rapidly in healthy subjects after oral administration and mainly eliminated from the kidney. No accumulation is observed after multiple dose administration. All the adverse events are mild and well tolerated. The results of PK/PD study indicate the regimen of 500 mg once a day might acquire ideal clinical and microbiological effect in patients with

关 键 词：左氧氟沙星 高效液相色谱法 药代动力学 药效学 不良事件 

分 类 号：R969.1[医药卫生—药理学] R978.19[医药卫生—药学]