Vol.70 No.6 November 2022
Open-label study of penetration of lascufloxacin into otorhinolaryngeal tissues (LSPOT study)
1)Department of Otorhinolaryngology, Yonaha Okanoue Hospital, 1-Sakuranooka, Kuwana, Mie, Japan
2)Department of Pharmacy, Yonaha Okanoue Hospital
3)Medical affairs, Clinical Development Center, Kyorin Pharmaceutical
Abstract
To evaluate the penetration of lascufloxacin (LSFX), an oral fluoroquinolone antibacterial agent, into otorhinolaryngeal tissues, we measured its concentrations in the nasal sinus mucosa (maxillary sinus mucosa, ethmoid sinus mucosa), middle ear mucosa, palatine tonsillar tissue, and plasma in patients who had undergone otorhinolaryngological surgery. The tissues and plasma were sampled 4 hours after the drug administration, when the tissue concentrations were expected to have reached their peak (jRCTs031200219).
The tissue concentrations of LSFX, the primary endpoint, were 1,322.0±373.9, 873.8±282.3, and 1,303.4±371.0 ng/g in the sinus mucosa, middle ear mucosa, and palatine tonsillar tissue, respectively. The plasma concentrations were 657.6±209.5 ng/mL when sinus mucosa concentrations were measured, 514.8±107.8 ng/mL when middle ear mucosa concentrations were measured, and 513.0±132.1 ng/mL when palatine tonsillar tissue concentrations were measured. Plasma concentrations were lower than the tissue concentrations. The tissue/plasma ratios of LSFX concentrations were 2.04±0.32, 1.66±0.24, and 2.53±0.21 for the sinus mucosa, middle ear mucosa, and palatine tonsillar tissue, respectively. We observed no adverse events that were potentially causally related to the study.
The tissue concentrations at 4 hours after LSFX administration (75 mg) were 1.6- to 5.0-fold higher than those at 1.5 hours (1.5±0.5 hours) reported previously. The tissue concentrations of LSFX at 4 hours after LSFX administration were >10-fold higher than the MIC90 of LSFX for the primary causative organisms of otorhinolaryngological infections. The tissue/plasma concentration ratios of LSFX increased by >2-fold from 1.5 to 4 hours after administration. The favorable tissue concentration of LSFX in otorhinolaryngological tissues confirms its usefulness in the current era, in which the main causative organisms of otorhinolaryngological infections are becoming increasingly resistant to antibacterial drugs.
Key word
lascufloxacin, otorhinolaryngological infection, tissue penetration
Received
August 5, 2022
Accepted
October 3, 2022
Jpn. J. Chemother. 70 (6): 445-452, 2022
