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Penetration of newer quinolones in the empyema fluid

¹ 2nd Dept of Surgery and ² Pneumonology, Medical School, Democritus University of Thrace, Alexandroupolis, and ³ Center of Toxicological Science and Research, Dept of Medicine, University of Crete, Heraklion, Greece. ⁴ Pulmonary Dept, Saint Thomas Hospital and Vanderbilt University, Nashville, TN, USA

CORRESPONDENCE: D.E. Bouros, Medical School, University of Thrace, Head, Dept of Pneumonology, University Hospital, Alexandroupolis 68100, Greece. Fax: 30 2551076106. E-mail: bouros@med.duth.gr

Keywords: Chromatography, Escherichia coli, levofloxacin, moxifloxacin, plural empyema, turpentine

Received: March 4, 2004
Accepted May 24, 2004

This study was supported by a grant from Abbott Laboratories (Hellas) and ELPEN SA Pharmaceuticals.

The degree of penetration of newer quinolones into the pleural fluid has not been studied. The objective of the present study was to determine the degree to which moxifloxacin and levofloxacin penetrate into empyemic pleural fluid using a new rabbit model of empyema.

An empyema was created via the intrapleural injection of turpentine (1 mL), followed 24 h later by instillation of 2 mL (1x10¹⁰) Escherichia coli bacteria (ATCC 35218) into the pleural space of New Zealand white rabbits. After an empyema was verified by thoracentesis and pleural fluid analysis, moxifloxacin and levofloxacin (25 mg·kg^–1 for both, i.v.) were administered. Antibiotic levels were determined in samples of pleural fluid and in blood collected serially over 12 h. Antibiotic levels were measured using HPLC.

Each of the antibiotics penetrated well into the empyemic pleural fluid. Antibiotic penetration was the greatest for moxifloxacin (area under the curve (AUC) for pleural fluid/blood (AUC_PF/AUC_blood) ratio=1.37) followed by levofloxacin (ratio=1.13). The time to equilibration between the pleural fluid and blood antibiotic levels was more rapid for moxifloxacin (3.9 h) than for levofloxacin (4.4 h). With moxifloxacin, the peak pleural fluid concentration (C_max,PF) was 2.77 µg·mL^–1 and occurred at a time to maximum pleural fluid concentration (T_max,PF) of 6 h after infusion and decreased thereafter. The peak blood concentration (C_max,blood) was 4.81 µg·mL^–1 at 1 h after administration. With levofloxacin, the peak pleural fluid level (C_max,PF=1.39 µg·mL^–1) occurred at 6 h (T_max,PF=6 h) after infusion. The C_max,blood was 1.88 µg·mL^–1 at 1 h after administration.

In conclusion, differences were found in the degree of penetration of the two quinolones into infected pleural fluid in rabbits. The clinical significance of these differences is unknown. More studies are needed to evaluate the pharmacokinetic parameters in the pleural space in humans.

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