CONCENTRATIONS OF OPC-17116, A NEW FLUOROQUINOLONE ANTIBACTERIAL, IN SERUM AND LUNG COMPARTMENTS

The efficacy oi an antibiotic is usually predicted from serum concentr ation and MICs for likely pathogens, but in the lung, tissue concentra tions may be more relevant. This study compares concentrations of a ne w fluoroquinolone, OPC-17116, in serum, epithelial lining fluid (ELF), alveolar macrophages and bronchial mucosa, in 24 adults. OPC-17116 40 0 mg was given daily for 4 days, and diagnostic bronchoscopy was perfo rmed up to 13h after the final dose. Mucosal biopsies were taken from macroscopically normal sites, alveolar macrophages were harvested by l avage, and ELF volume was derived from urea concentrations in bronchia l lavage fluid and blood. A microbiological assay, using Escherichia c oli, was used to assay OPC-17116 concentration in serum, bronchial muc osa, ELF and alveolar macrophages. The mean concentration of OPC-17116 in serum was 1.2 mg/L. Serum concentrations were significantly exceed ed in bronchial mucosa (mean ratio 3.13) in ELF (mean ratio 12.21) and in macrophages (mean ratio 194.52). Penetrations of these compartment s considerably exceeded those reported for other fluoroquinolones, and concentrations in all tissues were substantially higher than previous ly reported MIC(90) levels for a variety of bacteria, including Strept ococcus pneumoniae. A clinical role for OPC-17116 is suggested in a wi de range of respiratory infections, including those due to intracellul ar bacteria.