Concentration and penetration of nemonoxacin in bronchopulmonary tissues of patients undergoing pulmonary surgery: an observational PK study.

BACKGROUND

Nemonoxacin is a novel nonfluorinated quinolone with broad-spectrum antibacterial activity. It is indicated for the treatment of community-acquired pneumonia (CAP). This study was designed to characterize the pharmacokinetics (PK) and penetration of nemonoxacin in human bronchopulmonary tissues.

METHODS

Forty patients undergoing pulmonary surgery were enrolled and randomly assigned to one of the five groups according to the predefined timepoints of sampling. All patients received oral 500 mg nemonoxacin once daily for 3-5 consecutive days before surgery. Blood, lung tissue, bronchial mucosa, bronchial secretion, and bronchial cartilage samples were collected during surgery at 3 ± 1, 5 ± 1, 9 ± 1, 12 ± 2, or 24 ± 4 h following the last nemonoxacin dose. Nemonoxacin concentrations were determined and steady state PK profiles were calculated.

RESULTS

Nemonoxacin reached higher concentrations in lung tissues, bronchial mucosa, and bronchial secretions than in plasma. The tissue-to-plasma 24-h exposure ratio in lung tissue, bronchial mucosa, bronchial secretion, and bronchial cartilage was 4.15, 3.61, 2.13, and 0.62, respectively. The fAUC0-24/MIC in plasma, lung tissue, and bronchial mucosa against Streptococcus pneumoniae was 154.22, 640.45, and 556.82, respectively, which were much higher than the PK/PD targets. These results indicate that nemonoxacin has sufficient bronchopulmonary penetration for an antibacterial effect following multiple oral 500 mg doses in patients undergoing pulmonary surgery. Oral nemonoxacin 500 mg once daily is expected to achieve sufficient microbiological efficacy for CAP caused by S. pneumoniae.

CONCLUSION

The findings in this study further justify the recommended dosing regimen of nemonoxacin for CAP.

TRIAL REGISTRATION: This study was registered at www.chictr.org.cn (identifier ChiCTR1900022591).