Tomii Y, Ozaki M, Matsuda M, Honmura T, Nishimura I, Yamaguchi R, Adachi T, Okawa Y, Nishino T
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Arzneimittelforschung. 1996 Dec;46(12):1169-73.
The in vitro antibacterial activity of prulifloxacin (CAS 123447-62-1, NM441), a new quinoline prodrug, against clinical isolates from urinary tract infections was investigated. In addition, it was compared with ofloxacin (CAS 82419-36-1), levofloxacin (CAS 100986-85-4), ciprofloxacin urinary tract infections in mice, as well as its pharmacokinetics. 1. The antibacterial activity of NM394 (6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazeto[3,2- a]quinoline-3-carboxylic acid), an active metabolite of prulifloxacin, against gram-positive clinical isolates was inferior to that of levofloxacin and tosufloxacin, and equal to that of ofloxacin and ciprofloxacin. Against gram-negative clinical isolates, the activity of NM394 was superior to that of the reference drugs. 2. The therapeutic effect of prulifloxacin on experimental urinary tract infection with Escherichia coli in mice was equal to that of tosufloxacin and ciprofloxacin and superior to that of ofloxacin and levofloxacin. Its therapeutic effect on Pseudomonas aeruginosa infection was equal to that of tosufloxacin and ciprofloxacin, and superior to that of ofloxacin. Against urinary tract infection with olfloxacin-resistant Enterobacter cloacae, prulifloxacin was the most effective of all the drugs tested. 3. The maximal serum concentration of prulifloxacin was slightly higher than that of ciprofloxacin, and the area under the curve (AUC) for prulifloxacin was 1/4 that of ofloxacin, levofloxacin and tosufloxacin. The maximal concentration and AUC of prulifloxacin in lung and kidney were slightly higher than the corresponding values for ciprofloxacin but only 1/2 to 1/4 of the values for ofloxacin, levofloxacin and tosufloxacin. In conclusion, prulifloxacin (NM394) showed potent antibacterial activity against clinical isolates and potent therapeutic efficacy against experimental infection in spite of its lower AUCs compared with the reference drugs. These findings suggest that prulifloxacin may be a useful drug in the treatment of urinary tract infections.
对新型喹啉前体药物普卢利沙星（化学物质登记号123447 - 62 - 1，NM441）针对尿路感染临床分离菌株的体外抗菌活性进行了研究。此外，还将其与氧氟沙星（化学物质登记号82419 - 36 - 1）、左氧氟沙星（化学物质登记号100986 - 85 - 4）、环丙沙星在小鼠尿路感染模型中的情况以及其药代动力学进行了比较。1. 普卢利沙星的活性代谢产物NM394（6 - 氟 - 1 - 甲基 - 4 - 氧代 - 7 -（1 - 哌嗪基）- 4H - [1,3]噻唑并[3,2 - a]喹啉 - 3 - 羧酸）对革兰氏阳性临床分离菌株的抗菌活性低于左氧氟沙星和妥舒沙星，与氧氟沙星和环丙沙星相当。对革兰氏阴性临床分离菌株，NM394的活性优于参比药物。2. 普卢利沙星对小鼠实验性大肠杆菌尿路感染的治疗效果与妥舒沙星和环丙沙星相当，优于氧氟沙星和左氧氟沙星。其对铜绿假单胞菌感染的治疗效果与妥舒沙星和环丙沙星相当，优于氧氟沙星。针对耐氧氟沙星阴沟肠杆菌引起的尿路感染，普卢利沙星是所有受试药物中最有效的。3. 普卢利沙星的最大血清浓度略高于环丙沙星，其曲线下面积（AUC）是氧氟沙星、左氧氟沙星和妥舒沙星的1/4。普卢利沙星在肺和肾中的最大浓度和AUC略高于环丙沙星，但仅为氧氟沙星、左氧氟沙星和妥舒沙星相应值的1/2至1/4。总之，尽管与参比药物相比普卢利沙星的AUC较低，但它对临床分离菌株显示出强效抗菌活性，对实验性感染显示出强效治疗效果。这些研究结果表明普卢利沙星可能是治疗尿路感染的一种有用药物。
