Study objectives: The objectives of this study were to
characterize the single-dose and steady-state plasma pharmacokinetics
of IV levofloxacin and IV alatrofloxacin, and to compare the results to
pneumococcal isolate sensitivities in order to estimate the clinical
efficacy of current community-acquired pneumonia treatment regimens
against pneumococcal infections.
Two-way, open-label, randomized, crossover study.
Participants: Each of 12 healthy volunteer subjects
received IV levofloxacin, 500 mg qd for 7 days, and IV alatrofloxacin,
200 mg qd for 7 days. The two regimens were separated by a
2-week washout period.
Measurements and results:
Plasma concentration profiles were collected around the first
and final doses of both regimens and were assayed for their respective
quinolone concentrations. When the peak concentrations for both agents
were compared to standard twofold dilution minimum inhibitory
concentration (MIC) values for pneumococcal isolates, it was discovered
that the breakpoint MIC value at which each compound would no longer
achieve a peak plasma concentration/MIC ratio of at least 12:1 was 0.5
mg/L for levofloxacin and 0.25 mg/L for alatrofloxacin.
Conclusions: Based on the MIC that inhibits 90% of
isolates of Streptococcus pneumoniae for both of these
agents (1.0 to 2.0 mg/L for levofloxacin and 0.125 to 0.25 mg/L for
trovafloxacin), our results indicate that although the once-daily
regimen of alatrofloxacin appears to be appropriate for this pathogen,
a more aggressive regimen may need to be investigated to optimize the
clinical and microbiological effects of levofloxacin.