Bayesian反馈法研究左氧氟沙星在呼吸系统感染患者中药动学及药效学

Pharmacokinetics and pharmacodynamics of levofloxacin in patients with respiratory tract infections using Bayesian forecasting

目的研究两种给药方案中左氧氟沙星在呼吸系统感染患者中药动学特性.方法患者静脉输注左氧氟沙星200mg,一天二次(组1)或400mg,一天一次(组2),高效液相色谱法测定血中左氧氟沙星浓度;Bayesian反馈法拟合药动学参数.结果根据药-时数据得到组1和组2中左氧氟沙星峰浓度(Cmax)分别为(2.80±0.29)和(5.27±0.68)mg/L;AUC0～24分别为(30.1 7±4.06)和(37.81±7.50)(mg·h)/L;消除半衰期t1/2β为(7.104±0.36)和(7.37±0.21)h;表观分布容积(Vd)为(96.75±16.82)和(101.20±26.01)L;中央室分布容积(Vc)为(66.45±6.76)和(64.63±7.41)L;血清清除率(C1)为(148.47±41.43)和(142.04+25.40)ml/h.统计学处理结果表明两组间的Cmax和AUC0～24值有显著性差异(P＜0.001),t1/2β、Vd、Vc和Cl无差异(P＞0.05).药动学和药效学研究结果显示,两种给药方案中LVLX对于肺炎克雷伯菌、肠杆菌、变形菌、β-溶血链球菌、不动杆菌、嗜血杆菌、肺炎链球菌和厌氧菌的AUC0～24/MIC90值均大于30;对肺炎克雷伯菌和变形菌的AUC0～24/MIC90值大于240.结论组2的Cmax和AUC0～24/MIC90值均明显高于组1,且两组均未发生不良反应,组2的给药方案更方便.

Objective To study pharmacokinetics and pharmacodynamics of levofloxacin （LVLX） in patients with respiratory tract infections in two different administration. Method Patients were give LVLX 200mg twice a day （group 1） or 400mg once a day （group 2）. Serum drug concentrations were measured by HPLC. Bayesian forecasting method was used to estimate pharmacokinetic parameters of LVLX in patients with respiratory tract infections. Results Pharmacokinetic parameters of LVLX in Group 1 and Group 2 were calculated by Bayesian forecasting. Cmax were （2.80±0. 29）mg/L and （5.27±0. 68）mg/L respectively; area under the curve （AUC0-24）were （30. 17±4. 06）（mg· h）/L and （37.81±7.50）（mg· h）/L; elimination half-life （h/2β） （7.10±0. 36）h and （7.37±0. 21）h; apparent distribution volume （Vd） （96. 75±16.82）L and （101.20±26.01）L; central department distribution volume（Vc） （66.45±6.76）L and （64.63±7.41）L; and Clearance （C1） were （148. 47±41.43）ml/h and （142.04±25.40）ml/h, respectively. Statistical results showed that values of Cmax and AUC0-24 had significant difference （P〈0. 001）, but h/2β, Vd, Vc and C1 had not signifi- cant difference （P〉0.05）. The ratio of AUC0-24/MIC of LVLX against Klebsiella pneumoniae, Enterobacter spp. , Proteus spp. β-hemophilus Streptococcus, Acinetobacter, Hemophilus spp., Streptococcus pneumoniae and Anaerobe was more than 30, and against Klebsiella pneumoniae and Proteus spp. was more than 240 in two groups. Conclusion Cmax and AUC0-24/MIC90 of LVLX in group 2 were significantly higher than those in Group 1, and adverse drug reaction in two groups had been not found. Administration of Group 2 was beneficial to clinical treatment.