甲磺酸帕珠沙星氯化钠注射液健康志愿者单剂给药药动学.docVIP

甲磺酸帕珠沙星氯化钠注射液健康志愿者单剂给药药动学 【关键词】 ,,,甲磺酸帕珠沙星氯化钠注射液；,,,药动学；,,,健康志愿者 　　摘要： 目的 研究健康志愿者静脉滴注单剂甲磺酸帕珠沙星氯化钠注射液后药动学特征，为该药Ⅱ期临床试验提供依据。方法 采用2剂量2周期交叉试验设计。10名健康受试者单剂静脉滴注甲磺酸帕珠沙星氯化钠注射液300、500mg，HPLC法测其血清、尿药物浓度。结果 受试者静脉滴注甲磺酸帕珠沙星氯化钠注射液后，人体耐受良好，体内过程符合二室开放模型。主要药动学参数与给药剂量呈线性关系，cmax分别为83和1107μg/ml，AUC0-∞分别为1366和2404μg#12539;h/ml，V值分别为289和40L，t1/2β分别为177和227h，36h尿药累积回收率约为79%。结论 甲磺酸帕珠沙星氯化钠注射液静脉滴注血峰浓度高，组织分布较广，消除半衰期短，300mg每日2次可用于治疗敏感菌感染。 　　关键词： 甲磺酸帕珠沙星氯化钠注射液； 药动学； 健康志愿者 　　Pharmacokinetics of pazufloxacin mesylate sodium chloride injection　in healthy volunteers after a singledose administration 　　ABSTRACT Objective To study the pharmacokinetics of pazufloxacin mesylate sodium chloride injection in healthy volunteers after singledose administration. Method A singledose of 300 or 500mg pazufloxacin mesylate sodium chloride injection were administered venoclysisly to ten healthy volunteers in autocross test; the concentrations of pazufloxacin in serum and urine were detected by HPLC. Results Pazufloxacin was well tolerated. The concentrationtime data after single dose of 300 or 500mg pazufloxacin conformed to a twocompartment open model and there were linear relationship between dosages and major parameters, cmax were 83, 1107μg/ml respectively; AUC0-∞ were 1366, 2404 μg#12539;h/ml respectively; V were 289, 40L respectively; t1/2β were 177, 227h respectively. 79% of the administered doses were recovered in the urine within 36h. Conclusion These results indicate that pazufloxacin has a favorable pharmacokinetic properties with high blood concentration and good tissue distribution. 300mg twice daily dose may be used for the treatment of bacterial infections caused by susceptible organisms. 　　KEY WORDS Pazufloxacin mesylate sodium chloride injection; Pharmacokinetics; Healthy volunteer 　　甲磺酸帕珠沙星(pazufloxacin mesilate，PZLX)是日本富山化学公司开发的新喹诺酮类抗菌药，通过抑制细菌DNA拓扑异构酶活性而产生抗菌作用，对革兰阳性需氧菌、革兰阴性需氧菌及部分厌氧菌有良好抗菌作用，主要用于治疗呼吸道、泌尿道、皮肤及软组织等感染。单剂静脉输入400mg甲磺酸帕珠沙星，血峰浓度达985μg/ml， 24