In vivo evaluation of A-56619 (difloxacin) and A-56620: new aryl-fluoroquinolones.

Abstract

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.

• Authors: P B Fernandes, D T Chu, R R Bower, K P Jarvis, N R Ramer, N Shipkowitz
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 29 Issue 2 Pg. 201-8 (Feb 1986) ISSN: 0066-4804 [Print] United States
• PMID: 3521473 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Infective Agents
• Fluoroquinolones
• Piperazines
• Quinolines
• Ciprofloxacin
• difloxacin
• Norfloxacin
• sarafloxacin

Topics

• Animals
• Anti-Infective Agents
• Bacteria (drug effects)
• Bacterial Infections (drug therapy)
• Ciprofloxacin (analogs & derivatives)
• Enterobacteriaceae Infections (drug therapy)
• Escherichia coli Infections (drug therapy)
• Female
• Fluoroquinolones
• Half-Life
• Immunosuppression Therapy
• Klebsiella Infections (drug therapy)
• Mice
• Norfloxacin (pharmacology)
• Piperazines (metabolism, pharmacology, therapeutic use)
• Proteus Infections (drug therapy)
• Pseudomonas Infections (drug therapy)
• Pyelonephritis (drug therapy)
• Quinolines (metabolism, pharmacology, therapeutic use)
• Salmonella Infections, Animal (drug therapy)
• Staphylococcal Infections (drug therapy)
• Streptococcal Infections (drug therapy)