We have recently collaborated with other researchers (KA Rodvold, LH Danziger and M Gotfried) to investigate levofloxacin penetration into epithelial lining fluid (ELF), which is more indicative of penetration into sites of respiratory tract infections (RTIs) (9). Population PK analysis for levofloxacin revealed a very good fit of predicted-to-observed data for plasma concentrations, with an overall r2 value of 0.974.

There was also good correlation between the predicted and observed penetrations of levofloxacin into ELF, with an r2 value of 0.923 (9).

Therefore, predicted plasma and ELF concentrations of levofloxacin are very close to those observed. A Monte Carlo simulation was then performed to demonstrate the expected levofloxacin concentrations in ELF over 24 hr. This revealed that peak ELF concentrations after a levofloxacin 750 mg o.d. dose ranged from 25-27 mg/ml with a broad 95% CI (9).

Levofloxacin pulmonary concentrations using plasma data revealed a peak concentration of 12-13 mg/ml (9).

These data were then used to calculate the ratio of levofloxacin penetration into ELF to that into plasma, which was 1.161, demonstrating that slightly more drug gets to the primary infection site in ELF than in plasma (9).

A Monte Carlo simulation was then performed to assess the variability of penetration. The mean ELF/plasma penetration ratio was 3.18, and the median ratio was 1.43, indicating a large group of patients for whom a lot of drug penetrates out to the primary infection site. Over 61% of simulated patients achieved a penetration ratio > 1, and this in turn indicates that a large percentage of patients had AUC levels in ELF exceeding that in plasma (9).