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  • Title: In vivo evaluation of NM441, a new thiazeto-quinoline derivative.
    Author: Ozaki M, Matsuda M, Tomii Y, Kimura K, Segawa J, Kitano M, Kise M, Shibata K, Otsuki M, Nishino T.
    Journal: Antimicrob Agents Chemother; 1991 Dec; 35(12):2496-9. PubMed ID: 1667252.
    Abstract:
    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.
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