In vivo evaluation of NM441, a new thiazeto-quinoline derivative
In vivo evaluation of NM441, a new thiazeto-quinoline derivative
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新型噻氮喹啉衍生物 NM441 的体内评价
DOI：
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发表时间：
1991
影响因子：
4.9
通讯作者：
Takeshi Nishino
中科院分区：
文献类型：
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作者：
M. Ozaki;M. Matsuda;Y. Tomii;K. Kimura;J. Segawa;M. Kitano;M. Kise;K. Shibata;M. Otsuki;Takeshi Nishino
NM 441是一种新的噻唑喹啉羧酸衍生物NM 394的亲脂性前药，当口服给药时，它很容易被吸收并水解成其母体化合物。在以20 mg/kg的剂量对狗口服施用NM 441后，血浆中NM 394的峰值浓度为2.39微克/ml，而单独施用NM 394时为0.63微克/ml。在小鼠保护研究中，将NM 441的体内活性与环丙沙星、氧氟沙星和依诺沙星的体内活性进行比较。对全身金黄色葡萄球菌感染，NM 441与氧氟沙星一样有效，是环丙沙星的两倍。对于链球菌感染，NM 441的效果是氧氟沙星的2至3倍，是环丙沙星的5倍。对于大肠杆菌感染，NM 441与环丙沙星和氧氟沙星一样有效，但对于肺炎克雷伯氏菌、粘质沙雷氏菌和铜绿假单胞菌感染，NM 441的有效性是环丙沙星和氧氟沙星的2至4倍。在全身感染中，NM 441的有效性是依诺沙星的3至7倍。抗尿路感染的E.与环丙沙星和氧氟沙星相比，NM 441使每克肾脏的细菌CFU数减少了1至2 log 10，而铜绿假单胞菌减少了1至6 log 10。克雷伯氏菌对呼吸道感染有明显的抗感染作用。肺炎链球菌，NM 441与氧氟沙星一样有效，是环丙沙星的两倍。
NM441 is a lipophilic prodrug of a new thiazeto-quinoline carboxylic acid derivative NM394, and when it is administered orally it is readily absorbed and hydrolyzed to its parent compound. After oral administration of NM441 at a dose of 20 mg/kg to dogs, the peak concentration of NM394 in plasma was 2.39 micrograms/ml, whereas it was 0.63 micrograms/ml for NM394 administered alone. The in vivo activity of NM441 was compared with those of ciprofloxacin, ofloxacin, and enoxacin in mouse protection studies. NM441 was as effective as ofloxacin and was twice as effective as ciprofloxacin against systemic infection with Staphylococcus aureus. Against infections with streptococci, NM441 was two to three times as effective as ofloxacin and five times as effective as ciprofloxacin. Against infection with Escherichia coli, NM441 was as effective as ciprofloxacin and ofloxacin, but against infections with Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa, NM441 was two to four times as effective as ciprofloxacin and ofloxacin. NM441 was three to seven times as effective as enoxacin in systemic infections. Against urinary tract infections with E. coli, NM441 reduced the number of bacterial CFU per gram of kidney by 1 to 2 log10 more and, with P. aeruginosa, by 1 to 6 log10 more than did ciprofloxacin and ofloxacin. Against respiratory tract infections with K. pneumoniae, NM441 was as effective as ofloxacin and was twice as effective as ciprofloxacin.