Fernandes P B, Chu D T, Bower R R, Jarvis K P, Ramer N R, Shipkowitz N
Antimicrob Agents Chemother. 1986 Feb;29(2):201-8. doi: 10.1128/AAC.29.2.201.
A-56619 and A-56620 are two new aryl-fluoroquinolones which are as potent as or more potent than norfloxacin when administered orally and subcutaneously in mouse protection tests against Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. A-56619 and A-56620 were more potent than norfloxacin when administered orally against Escherichia coli, Proteus mirabilis, Serratia marcescens, and Pseudomonas aeruginosa. A-56620 was as potent or two- to threefold more potent than norfloxacin when administered subcutaneously against members of the family Enterobacteriaceae and Pseudomonas aeruginosa. Infection with Salmonella typhimurium was more effectively treated with A-56619 (50% effective dose [ED50], 1.4 mg/kg per day) than with norfloxacin (ED50, 62.8 mg/kg per day). E. coli or Pseudomonas pyelonephritis in mice was more effectively treated with A-56619 or A-56620 than with norfloxacin. After oral treatment, the ED50s of A-56619 and A-56620 were less than 12.5 mg/kg per day against E. coli and 62.9 and 38 mg/kg per day against P. aeruginosa pyelonephritis, respectively. Norfloxacin was ineffective at 200 mg/kg per day against E. coli or P. aeruginosa pyelonephritis. A-56619 and A-56620 were also more potent than norfloxacin in treatment of mixed bacterial pyelonephritis caused by E. coli and Streptococcus faecalis. A-56619 was at least 30 times more potent than norfloxacin and A-56620 was 4 to 11 times more potent than norfloxacin when administered against Klebsiella pneumonia in mice. A-56619 and A-56620 were at least 2 to 10 times more potent than norfloxacin against Staphylococcus aureus infections in immunosuppressed mice. A-56619 was equally potent in all in vivo tests when administered orally or subcutaneously, whereas A-56620 was similar to norfloxacin in being more potent when administered subcutaneously. The peak serum levels after subcutaneous and oral administration of A-56619 and A-56620 were higher than that of norfloxacin. The serum hal-lives of A-56619 and A-56620 after subcutaneous and oral administration were longer than the serum half-life of norfloxacin.
A - 56619和A - 56620是两种新型芳基氟喹诺酮类药物，在针对金黄色葡萄球菌、化脓性链球菌和肺炎链球菌的小鼠保护试验中，口服和皮下给药时，它们的效力与诺氟沙星相当或更强。口服给药时，A - 56619和A - 56620对大肠杆菌、奇异变形杆菌、粘质沙雷氏菌和铜绿假单胞菌的效力比诺氟沙星更强。皮下给药时，A - 56620对肠杆菌科成员和铜绿假单胞菌的效力与诺氟沙星相当或强两到三倍。用A - 56619（半数有效剂量[ED50]，每天1.4毫克/千克）治疗鼠伤寒沙门氏菌感染比用诺氟沙星（ED50，每天62.8毫克/千克）更有效。用A - 56619或A - 56620治疗小鼠的大肠杆菌或铜绿假单胞菌肾盂肾炎比用诺氟沙星更有效。口服治疗后，A - 56619和A - 56620对大肠杆菌的ED50分别小于每天12.5毫克/千克，对铜绿假单胞菌肾盂肾炎的ED50分别为每天62.9毫克/千克和38毫克/千克。诺氟沙星每天200毫克/千克对大肠杆菌或铜绿假单胞菌肾盂肾炎无效。在治疗由大肠杆菌和粪肠球菌引起的混合细菌性肾盂肾炎方面，A - 56619和A - 56620也比诺氟沙星更有效。在针对小鼠肺炎克雷伯菌给药时，A - 56619的效力至少比诺氟沙星强30倍，A - 56620的效力比诺氟沙星强4至11倍。在免疫抑制小鼠中，A - 56619和A - 56620对金黄色葡萄球菌感染的效力至少比诺氟沙星强2至10倍。口服或皮下给药时，A - 56619在所有体内试验中的效力相同，而A - 56620与诺氟沙星相似，皮下给药时效力更强。皮下和口服给予A - 56619和A - 56620后的血清峰值水平高于诺氟沙星。皮下和口服给予A - 56619和A - 56620后的血清半衰期长于诺氟沙星的血清半衰期。
