Diffusion of Oral and Intravenous 400 mg Once-Daily Moxifloxacin into Lung Tissue at Pharmacokinetic Steady-State

Abstract

The degree of penetration of an antibiotic into the infection site is an important factor for its therapeutic efficacy, particularly in respiratory tract infections. In the present study, we examined the lung tissue diffusion of moxifloxacin at a dose of 400 mg administered intravenously or orally once-daily, and the results were correlated to microbiological data to estimate the clinical efficacy of moxifloxacin in lower community-acquired respiratory infections. This was a prospective, randomized, parallel-group trial, open-label, single-center study. Patients undergoing lung surgery for bronchial cancer which necessitates the removal of an anatomical piece of lung tissue were randomized into twelve treatment groups, dependent upon the time of surgery and the moxifloxacin formulation, i.v. or oral, administered. During surgery, one blood sample was taken at the time of tissue collection to determine moxifloxacin plasma concentration. At the same time, tissue samples were taken by pulmonary exeresis. A validated new high performance liquid chromatography assay was used to determine moxifloxacin concentrations in plasma and lung tissue. A total of 49 patients (25 for i.v. administration, 24 for oral administration, 44 men and 5 women, mean age, 61 years, mean body weight, 72 kg, mean creatinine clearance was 84 ml/min/1.73 m²) were enrolled. The mean ± SD steady-state moxifloxacin ratios between lung and plasma concentrations were respectively: 3.53 ± 1.89 and 4.36 ± 1.48 for i.v. and oral administration.

The mean steadystate moxifloxacin maximal lung concentrations (Cmax) were respectively 12.37 μg/g and 16.21 μg/g for i.v. and oral administration. Moxifloxacin both intravenously and orally exhibits high penetration in lung tissue, with tissue concentrations far above the MIC_90s for most of the susceptible pathogens commonly involved, thus underlining its suitability for the treatment of community-acquired, lower respiratory tract infections.