Question 1

What are the pharmacokinetic features of the 750 mg levofloxacin dose that make it an attractive therapeutic strategy in comparison to the 500 mg dose?

It is well known that levofloxacin is a concentration-dependent agent which is rapidly bactericidal, with exceptional oral bioavailability and linear pharmacokinetics allowing the same dose to be used orally or intravenously. As expected, this remains a feature of the higher dose, with the 750 mg regimen possessing the added benefit of achieving and maintaining greater plasma concentrations throughout a 24 hour period (Figure 1).

In addition, higher peak concentrations translate into more antibacterial agent available at the site of infection and enhanced pathogen killing. It has also been demonstrated that, 2-4 hours after oral administration, the concentrations achieved in tissues such as epithelial lining fluid (ELF) or alveolar macrophages can exceed that recorded in plasma – an important advantage whereby levofloxacin is able to achieve high concentrations within tissues making it an effective agent for targeting atypical intracellular pathogens (2).

^a In healthy volunteers who received a single dose.
Abbreviation: IV = intravenous.
Adapted from reference (1).