In vivo comparative pharmacokinetics and pharmacodynamics of moxifloxacin and levofloxacin in human neutrophils

Abstract

Objective: Most of the newer fluoroquinolones are active against bacteria such as Streptococcus pneumoniae and Staphylococcus aureus, which are able to multiply inside polymorphonuclear leukocytes (PMNs). The aim of this study was to determine moxifloxacin and levofloxacin intracellular behaviour with their usual dosage regimen.

Methods: We determined the pharmacokinetics of moxifloxacin and levofloxacin at steady state in the PMNs of ten healthy volunteers receiving moxifloxacin 400mg and levofloxacin 500mg as a once-daily dosing regimen for 3 days.

Results: Both antibacterials showed a high level of intracellular penetration exhibiting PMNs/plasma ratios of 17.34 +/- 8.29 for moxifloxacin versus 8.15 +/- 5.23 for levofloxacin for maximum concentrations (C(max)) and 14.72 +/- 8.29 for moxifloxacin versus 8.15 +/- 5.23 for levofloxacin for the area under the plasma concentration-time curve. Estimation of the most predictive pharmacodynamic surrogate markers for concentration-dependent bactericidal antibacterials in the intracellular milieu by taking into account the susceptibility of S. pneumoniae and methicillin-susceptible S. aureus demonstrated consistently higher values with moxifloxacin than with levofloxacin, even though with both drugs the levels obtained are well above the recommended targets values. Indeed, C(max)/MIC ratios calculated in PMNs for moxifloxacin were 287.3 and 718.2 for S. pneumoniae and S. aureus, respectively, and for levofloxacin were 25.6 and 205.1, respectively.

Conclusion: Moxifloxacin and levofloxacin seem to be well adapted for the treatment of infections due to susceptible intracellular bacteria, and moxifloxacin provides a greater margin of safety than levofloxacin.