Penetration of garenoxacin into lung tissues and bone in subjects undergoing lung biopsy or resection

ABSTRACT

Objective: Concentrations of garenoxacin in plasma and samples of lung parenchyma, bronchial mucosa, and bone were determined following single-dose administration.

Research design and methods: Open-label, non-randomized study in which subjects undergoing invasive lung biopsy or resection were given a single 600‑mg oral dose of garenoxacin. Lung parenchyma, and, if possible, bronchial mucosa and bone (i.e., flat bone with sinus mucosa or long bone from the lower legs) samples and corresponding plasma samples were obtained 2–4, 4–6, 10–12, or 20–24 h post-dose. Garenoxacin concentrations were measured using validated liquid chromatography with dual mass spectrometry. Safety was also assessed.

Results: Twenty-seven subjects enrolled and completed the study. Garenoxacin plasma concentrations (mean ± standard deviation) during the 24‑h period ranged from 1.9 ± 1 to 7.4 ±3 µg/mL. Garenoxacin concentrations in lung tissue (15.2 ± 9 µg/g) peaked at 4–6 h and decreased to 3.7 ± 3 µg/g at 20–24 h. Mean ratios between bronchial mucosa and plasma ranged from 0.82 to 0.99 over a 24-h period. At 12 h, the mean ratio between bone and plasma was 0.56. Garenoxacin concentrations in lung tissue exceeded the MIC₉₀ for common respiratory pathogens by at least 61-fold. Garenoxacin was safe and well tolerated. Forty-five adverse events were reported by 26 subjects; none were determined to be attributable to garenoxacin by the investigators. Most of the adverse events were mild to moderate in severity.

Conclusions: Garenoxacin achieved 24-h concentrations in pulmonary tissues that exceeded the MIC₉₀ for common respiratory pathogens. A controlled study involving a larger number of lung and bone tissue samples is needed to further confirm these findings.

Key words: :

• Garenoxacin
• Lung
• Quinolones
• Tissue distributions