甲磺酸帕珠沙星注射液人体药动学研究.docVIP

甲磺酸帕珠沙星注射液人体药动学研究 作者：沈奇 梁德荣 苗佳 余勤 梁茂植 徐楠 郑莉 罗柱 吴松泽 【摘要】 目的 研究单次及多次静脉滴注甲磺酸帕珠沙星注射液的药动学特点。方法 筛选健康受试者12名，q12h静脉滴注甲磺酸帕珠沙星注射液每次500mg，连续5d，共9次；用反向高效液相色谱紫外法测定血药浓度，用DASver1.0软件拟合药动学参数。结果 受试者静脉滴注甲磺酸帕珠沙星注射液后体内过程符合二室模型；单次给药后的药动学参数：Tmax为(0.47±0.09)h，cmax为(13.71±1.81)mg/L，AUC0-t为(24.60±4.15)mg·h/L，t1/2为(1.46±0.64)h，MRT、CL和Vd分别为(2.14±0.33)h、(0.09±0.04)L/(h·kg)和(0.17±0.03)L/kg。q12h静脉滴注帕珠沙星500mg连续5d(共9次)，第2、3、4、5d晨测得谷浓度分别为0.13、0.16、0.17和0.14mg/L，提示血药浓度已达稳态。末剂给药后的药动学参数：Tmax为(0.48±0.10)h，cmax为(15.41±1.67)mg/L，AUC0-t为(28.42±4.90)mg·h/L，t1/2为(1.33±0.49)h，CL为(0.09±0.06L/)h，(css)av为(2.34±0.43)mg/L，DF为(99.48±0.38)%，以上参数与单次给药比较除cmax外均无统计学差异，且累积系数小，说明本品多次给药无体内蓄积。女性和男性受试者主要药动学参数比较均无统计学差异。受试者给药期间未出现严重不良反应。结论 500mg q12h静脉滴注，在人体内可达到有效血药浓度，可以作为临床应用的推荐方案。 【关键词】 甲磺酸帕珠沙星； 反向高效液相色谱紫外法； 药动学 　　Study on pharmacokinetics of pazufloxacin mesylate injection　in healthy volunteers 　　ABSTRACT Objective To investigate the pharmacokinetics of pazufloxacin mesylate injection after single and multipledoses intravenously. Methods Twelve healthy volunteers were administrated 500mg pazufloxacin mesylate twice a day for 5 days. The plasma concentrations were determined by RPHPLCUV method and the pharmacokinetic parameters were calculated by DASver1.0 software. Results The pharmacokinetics of pazufloxacin is fit to two compartment model. The pharmacokinetic parameters after single administration: Tmax was (0.47?.09)h, cmax was (13.71?.81)mg/L, AUC0-t was (24.60?.15)mg穐/L, t1/2 was (1.46?.64)h, MRT was (2.14?.33)h, CL was (0.09?.04)L/(h穔g) and Vd was (0.17?.03)L/kg. The pharmacokinetic parameters after successive administration: Tmax was (0.48?.10)h, cmax was (15.41?.67)mg/L, AUC0-t was (8.42?.90)mg穐/L, t1/2 was (1.33?.49)h, CL was (0.09?.06)L/h, (css)av was (2.34?.43)mg/L, DF was (99.48?.38)%. There were no significant differences in all pharmacokinetic parameters except cmax between the first and the last administraion of pazufloxacin and cumulatio