Abstract
Levofloxacin is a major antimicrobial agent that is used for the treatment of community-acquired lower respiratory tract infections (LRTIs). The present study was designed to investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of levofloxacin in bronchial mucosa and lung tissue. A total of 32 patients undergoing pulmonary surgery were randomly assigned to one of four groups (8 subjects/group). All patients received a single dose of 500 mg levofloxacin orally prior to the operation. Blood, lung tissue and bronchial mucosa samples were collected prior to treatment and at 1.5, 4, 8, 12 and 24 h following treatment. The drug concentration was determined and PK and PD profiles were calculated using MATLAB software. The peak concentration of levofloxacin was 7.0±1.2 µg/g in lung tissues and 9.4±2.1 µg/g in bronchial mucosa. The corresponding area under the curve between 0 and 24 h (AUC(0-24)) was 85.7±8.5 and 137.3±19.4 µg h/g. The mean permeability of levofloxacin (ratio of concentration in tissue to that in plasma) was 2.4 in lung tissue and 4.4 in the bronchial mucosa. The PK profiles of levofloxacin in the plasma, lung and bronchial mucosa were described using an integrated one-compartment model. The probability of fAUC(0-24)/minimal inhibitory concentration (MIC) target attainment of levofloxacin against Streptococcus pneumoniae in the lung and bronchial mucosa was maintained at 100% when MIC ≤1 mg/l, while the cumulative fraction of fAUC(0-24)/MIC in the corresponding tissues was 94.4 and 98.1%, respectively. The present study demonstrated the high permeability of levofloxacin in the lung and bronchial mucosa of patients undergoing pulmonary surgery. In conclusion, treatment using 500 mg levofloxacin exhibits good clinical and microbiological efficacy for use in LRTIs that are caused by S. pneumoniae. This trial was registered retrospectively in the Chinese Clinical Trial Registry on January 13, 2020 (registration no. ChiCTR2000029096).