Chemotherapeutic activity of levofloxacin (HR 355, DR-3355) against systemic and localized infections in laboratory animals

Abstract

Ofloxacin, its optical isomers levofloxacin (HR 355, DR-3355) and D-ofloxacin (DR-3354) and ciprofloxacin were administered orally to mice and rats which had systemic and localized infections. Both levofloxacin and ciprofloxacin were equally effective in treating systemic murine infections caused by staphylococci. Enterobacteriaceae or Pseudomonas aeruginosa with ED50s ranging from 0.18 to 15.8 mg/kg and 0.42 to 16.3 mg/kg respectively and both these agents were twice as effective as ofloxacin which had an ED50 0.41 to 39.7 mg/kg. In contrast, D-ofloxacin was either inactive or exhibited only modest chemotherapeutic activity against the staphylococci and the Gram-negative organisms tested. When given to mice to treat staphylococcal abscesses and lung infections due to Klebsiella pneumoniae DT-S levofloxacin was up to four times more effective and produced a more pronounced bactericidal effect against the pathogens in vivo than the reference compounds. Despite possessing a similar, if not lesser, in-vitro activity against the infecting pathogens, levofloxacin was more effective than ofloxacin and ciprofloxacin in rats with localized infections caused by Enterobacteriaceae and P. aeruginosa.

The Nonantibiotic Macrolide EM703 Improves Survival in a Model of Quinolone-Treated Pseudomonas aeruginosa Airway Infection

“…1A). Based on the literature, a levofloxacin dose of 100 mg/kg was chosen to rapidly achieve complete bacterial killing and resulting high levels of release of bacterial components (22)(23)(24)(25). The MIC of levofloxacin against P. aeruginosa (strain PAO1) is 0.25 g/ml.…”

Bactericidal Activities of BMS-284756, a Novel Des-F(6)-Quinolone, against Staphylococcus aureus Strains with Topoisomerase Mutations

“…Upon testing the parental MT5 in vivo, the resulting PD 50 s of levofloxacin were unusually high compared to published values for other wild-type strains of S. aureus (6,13). The PD 50 s of the MT5224c4 and EN8 mutants, therefore, were irregular or could not be calculated from the high concentrations of quinolone tested.…”

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Levofloxacin

“…88 Because the LD 50 in rats is 1500 mg/kg 13 and the ED 50 range in rats is 0.18-16.3 mg/kg, 89 resulting in an almost 10-fold difference, and there is generally no need to monitor blood levels, levofloxacin can be considered as a wide therapeutic index drug, according to the US FDA. 88 Furthermore, Health Canada published a guidance including drugs which commonly exhibit adverse effects that limit the therapeutic use to doses close to those required for the therapeutic effect (e.g., "narrow therapeutic range drugs") or drugs for which the therapeutic use may result in dose or concentrationdependent adverse effects, which are persistent, irreversible or slowly-reversible, or life threatening (e.g., "highly toxic drugs"), and this list does not include levofloxacin.…”