Penetration of garenoxacin into lung tissues and bone in subjects undergoing lung biopsy or resection.
OBJECTIVE
Concentrations of garenoxacin in plasma and samples of lung parenchyma, bronchial mucosa, and bone were determined following single-dose administration.


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 mug/mL. Garenoxacin concentrations in lung tissue (15.2 +/- 9 mug/g) peaked at 4-6 h and decreased to 3.7 +/- 3 mug/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 MIC(90) 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 MIC(90) for common respiratory pathogens. A controlled study involving a larger number of lung and bone tissue samples is needed to further confirm these findings.
Krishna
Gopal
G
Department of Pharmacokinetics and Early Clinical Research & Experimental Medicine, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. Gopal.Krishna@spcorp.com <Krishna@spcorp.com>
Gotfried
Mark H
MH
Rolston
Kenneth
K
Wang
Zaiqi
Z
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001706:Biopsy; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C419689:garenoxacin