Concentrations of oral lomefloxacin in serum and bronchial mucosa

Abstract

The bronchial mucosal concentrations of lomefloxacin were determined for specimens obtained by fiber-optic bronchoscopy and compared with simultaneous concentrations in serum. The 23 patients studied were given an oral dose of 400 mg once daily for 4 days to achieve steady-state levels. The median concentration in serum was 2.5 ,ug/ml (range, 1.0 to 5 ,ug/ml), and the median bronchial mucosal concentration was 5.0 ,ug/g (range, 0.7 to 18.6 ,Lg/g). The median percent penetration was 177% (range, 69 to 541%). The concentrations in serum and mucosa exceeded the MIC for 90% of strains of organisms causing bronchial infections but not sufficiently to recommend lomefloxacin for the routine treatment of pneumococcal infections.The likely clinical efficacy of antibiotics may be predicted from the concentrations of the agent in the tissues and secretions which are the usual sites of infection. In the respiratory tract, antibiotic concentrations in sputum have been determined, but these can be unreliable (1, 13). The bronchial mucosa is probably the main site of acute bacterial infection in patients with chronic bronchitis and bronchiectasis (5) and, therefore, it is reasonable to measure drug concentrations at this site. Several quinolones have been found to attain higher bronchial mucosal and lung tissue concentrations than simultaneous concentrations in serum (7,9,17). The aim of this study was, therefore, to assess the concentration of a new quinolone, lomefloxacin, in human bronchial mucosa.Lomefloxacin is a fluoroquinolone with a broad spectrum of in vitro activity against clinically important gram-positive and gram-negative aerobes and anaerobes, including the majority of organisms responsible for lower respiratory tract infections, including Staphylococcus aureus (18). Like the other quinolones, it also has activity against Legionella pneumophila and Mycoplasma pneumoniae (6). It has a prolonged serum half-life, and it is therefore appropriately given as a once-daily dose (16). MATERIALS AND METHODSA total of 23 patients (14 male and 9 female) undergoing fiber-optic bronchoscopy for diagnostic purposes were studied. The indication for bronchoscopy was focal radiological abnormality in 19 patients and hemoptysis in 4 patients. The final diagnosis was squamous cell carcinoma in seven patients, and in the remainder, no abnormality was found. Ages ranged from 40 to 65 years (mean, 57 years). Lomefloxacin was self-administered in a dose of 400 mg once daily, in the morning, for 4 days, with the final dose of lomefloxacin given on the morning of the bronchoscopy, making a total of 4 doses. A standard premedication of 160 mg of 4% nebulized lignocaine, 0.6 mg of intramuscular atropine, and 2.5 to 5 mg of intravenous midazolam was used. Bronchial biopsies were taken from the subcarinae of macroscopically normal bronchi (absence of erythema, nodularity, or edema) and immediately placed in a humidity chamber. Any specimens macroscopically contaminated * Corresponding author. with blood were discarded. A serum sample for det...

Transepithelial transport of the fluoroquinolone ciprofloxacin by human airway epithelial Calu-3 cells

“…Metabolite concentrations in all tissues assayed (lung, bronchial mucosa, and pleural tissue) are low compared to ciprofloxacin concentrations (20). The fluoroquinolone ofloxacin also penetrates well into human lung tissue (22), as do enoxacin (25) and lomefloxacin (2). This means that, unlike aminoglycosides and ␤-lactams, which are excluded from intracellular infection sites, fluoroquinolones are efficient in the treatment of respiratory infections (17), which can be caused by both intracellular and extracellular pathogens (18).…”

Lomefloxacin Clinical Pharmacokinetics

“…The majority of microassays for lomefloxacin have used Escherichia coli as the test organism (Baldwin et al 1990;Bergogne-Berezin et al 1992;Leigh et al 1991;Leroy et al 1990Leroy et al , 1992Shibl et al 1991;Stone et al 1988;Wise et al 1991). The majority of microassays for lomefloxacin have used Escherichia coli as the test organism (Baldwin et al 1990;Bergogne-Berezin et al 1992;Leigh et al 1991;Leroy et al 1990Leroy et al , 1992Shibl et al 1991;Stone et al 1988;Wise et al 1991).…”

Steady-state pharmacokinetics and sputum penetration of lomefloxacin in patients with chronic obstructive pulmonary disease and acute respiratory tract infections

“…It appears that some variation exists in the bronchopulmonary disposition of currently available quinolones (7,10). The concentration of lomefloxacin in bronchial mucosal tissue has been assessed in patients undergoing bronchoscopy; the median steady-state concentration was 177% that of serum (1). Its penetration into purulent infected sputum, however, has not been evaluated.…”