Penetration of orally administered prulifloxacin into human lung tissue

To evaluate the distribution in lung tissue of ulifloxacin, the active metabolite of prulifloxacin, a new once-daily fluoroquinolone administered orally in a single 600mg dose.

Open-label, randomised study.

Twenty-seven patients (25 males, 2 females; mean age 65.7 years [range 49-79 years]) with a lung neoplasm requiring lobectomy or pneumonectomy.

Patients were randomly assigned to five treatment groups and received a single oral dose of prulifloxacin 600mg at 2, 4, 6, 12 or 24 hours preoperatively. During surgery, blood and healthy lung (based on macroscopic appearance) samples were collected at the same time. Ulifloxacin concentrations in plasma and lung tissue were determined by a validated reversed-phase high-performance liquid chromatography assay. Lung tissue ulifloxacin concentrations were adjusted for blood contamination, by measuring haemoglobin in the supernatant of each tissue sample and applying a corrective equation.

Ulifloxacin concentration in lung tissue exceeded plasma concentration at every timepoint. Following administration of prulifloxacin 600mg, the overall mean corrected lung/plasma ratio over the 24-hour period was 6.9 (range 1.2-14.1). When sampling intervals were assessed, the corrected lung/plasma ratios were 7.5 (2 hours after dosing), 6.3 (4 hours), 4.3 (6 hours), 7.0 (12 hours) and 9.2 (24 hours). The mean corrected lung/plasma area under the concentration-time curve ratio was 6.3, demonstrating the ability of the drug to penetrate lung tissue and confirming the high exposure of this target tissue to ulifloxacin. However, the limitation of the lung tissue sampling method and the high interpatient variability should be considered. Over the 24-hour period, the concentrations of ulifloxacin in lung tissue were higher than the minimum inhibitory concentration (MIC) values for pathogens frequently involved in community-acquired respiratory tract infections.

Lung tissue penetration data may have a supportive value when considered jointly with MICs and efficacy results. The findings from this lung penetration study could explain the efficacy of once-daily prulifloxacin 600mg observed in clinical trials conducted in patients with exacerbation of chronic bronchitis.