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Concentrations of OPC-17116, a new fluoroquinolone antibacterial, in serum and lung compartments.

The efficacy of an antibiotic is usually predicted from serum concentration and MICs for likely pathogens, but in the lung, tissue concentrations may be more relevant. This study compares concentrations of a new fluoroquinolone, OPC-17116, in serum, epithelial lining fluid (ELF), alveolar macrophages and bronchial mucosa, in 24 adults. OPC-17116 400 mg was given daily for 4 days, and diagnostic bronchoscopy was performed up to 13 h after the final dose. Mucosal biopsies were taken from macroscopically normal sites, alveolar macrophages were harvested by lavage, and ELF volume was derived from urea concentrations in bronchial lavage fluid and blood. A microbiological assay, using Escherichia coli, was used to assay OPC-17116 concentration in serum, bronchial mucosa, ELF and alveolar macrophages. The mean concentration of OPC-17116 in serum was 1.2 mg/L. Serum concentrations were significantly exceeded in bronchial mucosa (mean ratio 3.13) in ELF (mean ratio 12.21) and in macrophages (mean ratio 194.52). Penetrations of these compartments considerably exceeded those reported for other fluoroquinolones, and concentrations in all tissues were substantially higher than previously reported MIC90 levels for a variety of bacteria, including Streptococcus pneumoniae. A clinical role for OPC-17116 is suggested in a wide range of respiratory infections, including those due to intracellular bacteria.