左氧氟沙星在重症社区获得性肺炎患者中的药物动力学研究

目的:比较左氧氟沙星治疗重症肺炎的不同用药方案的药物动力学差异,为临床合理用药提供依据.方法:24例成人重症社区获得性肺炎且正在接受机械通气的患者分为两组(n=12),分别每日1次或2次静脉滴注左氧氟沙星500 mg,同时每日滴注1次拉维酸1 g,连续静脉滴注10 d,经过2d的治疗达到稳定状态后利用高效液相色谱法测定血浆和上皮细胞衬液中左氧氟沙星的浓度,并比较两组间药动学参数.结果:每日滴注1次的患者,左氧氟沙星的血浆值浓度和上皮细胞衬液浓度分别为(12.6±2.3) mg/L和(11.9±2.7) mg/L,每日滴注2次的患者分别为(19.7±1.8) mg/L和(17.8±1.7) mg/L,这表明左氧氟沙星在肺组织的穿透率都大于100％.每日滴注1次和2次的患者全身暴露浓度(AUC24h)分别为(151.2±12.8) mg· h· L-1和(208.6±15.1) mg· h· L-1,均高于常见重症肺炎致病菌的最小抑菌浓度(MIC).每日滴注1次组的治疗成功率为83％(10/12),每日滴注2次组为92％(11/12),无统计学差异(P＞0.05).结论:对因重症社区获得性肺炎接受机械通气的危重患者,每日静脉滴注500mg左氧氟沙星1次或2次均能达到最小的抑菌浓度.

Pharmacokinetics and intrapulmonary diffusion of levofloxacin in critically ill patients with severe community-acquired pneumonia

AIM To compare the different medication regimens of levofloxacin in treatment of community-acquired pneumonia and provide evidence for clinical rational drug use. METHODS Twenty-four adult patients with severe community-acquired pneumonia and receiving mechanical ventilation were assigned randomly into 2 groups （ n=12） received 1-hour intravenous infusion of levotloxacin 500 mg once or twice daily respectively. The levotloxacin concentrations at steady-state in plasma and epithelial lining fluid were determined with high-performance liquid chromatography after 2 days of therapy. The pharmacokinetics was calculated and compared. RESULTS Levotloxacin concentrations in plasma and epithelial lining fluid peak were （12.6±2.3）mg·L^-1 and （11.9 ±2.7）mg·L^-1 respectively in the once-daily group and（19.7 ±1.8） mg·L^-1 and（17.8±1.7）mg·L^-1 in the twice-daily group, showing pulmonary penetration percentage 〉100% in both groups. The total body exposure （AUC24h）in the once-daily and twice-daily group was（151.2±12.8）mg·h·L^-1 and（208.6±15.1）mg·h·L^-1 respectively, each higher than the minimal inhibitory concentration for severe pneumonia. The treatment success rate in the once-daily and twice-daily group was 83%（10/12）and 92%（11/12）with no significant difference（P〉0.05）. CONCLUSION For critically ill patients with severe community-acquired pneumonia and receiving mechanical ventilation, the administration of intravenous levofloxacin 500 mg once and twice daily all can reach the minimal inhibitory concentration.