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Pharmacology

Intrapulmonary Pharmacokinetics of Lascufloxacin in Healthy Adult Volunteers

Hidetoshi Furuie, Sayoko Tanioka, Keiko Shimizu, Shigeru Manita, Masaharu Nishimura, Hisao Yoshida
Hidetoshi Furuie
aOsaka Pharmacology Clinical Research Hospital, Osaka, Japan
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Sayoko Tanioka
bKyorin Pharmaceutical Co., Ltd., Tokyo, Japan
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Keiko Shimizu
cWatarase Research Center, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan
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Shigeru Manita
cWatarase Research Center, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan
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Masaharu Nishimura
dDepartment of Respiratory Medicine, Faculty of Medicine (and Graduate School of Medicine), Hokkaido University, Sapporo, Japan
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Hisao Yoshida
bKyorin Pharmaceutical Co., Ltd., Tokyo, Japan
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DOI: 10.1128/AAC.02169-17
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ABSTRACT

This study was performed to investigate the intrapulmonary penetration of lascufloxacin in humans. Thirty healthy adult male Japanese subjects, allocated into five groups, received lascufloxacin in a single oral dose of 75 mg. Bronchoalveolar lavage and blood sampling were performed simultaneously in each subject at 1, 2, 4, 6, or 24 h after administration, and lascufloxacin concentrations in plasma, epithelial lining fluid, and alveolar macrophages were determined. Lascufloxacin was rapidly distributed to the epithelial lining fluid with a time to maximum drug concentration (Tmax) of 1 h, which was identical to that in plasma. The maximum concentration of drug (Cmax) values in plasma, epithelial lining fluid, and alveolar macrophages were 0.576, 12.3, and 21.8 μg/ml, respectively. The corresponding area under the concentration-time curve from 0 to 24 h (AUC0–24) values were 7.67, 123, and 325 μg · h/ml. The mean drug concentrations in the epithelial lining fluid and alveolar macrophages were much higher than those in plasma at all time points examined, and the average site-to-free plasma concentration ratios fell within the ranges of 57.5 to 86.4 and 71.0 to 217, respectively. Drug levels in epithelial lining fluid and alveolar macrophages exceeded the MIC90 values for common respiratory pathogens. (This study was registered at JAPIC under registration number JapicCTI-142547.)

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Intrapulmonary Pharmacokinetics of Lascufloxacin in Healthy Adult Volunteers
Hidetoshi Furuie, Sayoko Tanioka, Keiko Shimizu, Shigeru Manita, Masaharu Nishimura, Hisao Yoshida
Antimicrobial Agents and Chemotherapy Mar 2018, 62 (4) e02169-17; DOI: 10.1128/AAC.02169-17

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Intrapulmonary Pharmacokinetics of Lascufloxacin in Healthy Adult Volunteers
Hidetoshi Furuie, Sayoko Tanioka, Keiko Shimizu, Shigeru Manita, Masaharu Nishimura, Hisao Yoshida
Antimicrobial Agents and Chemotherapy Mar 2018, 62 (4) e02169-17; DOI: 10.1128/AAC.02169-17
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KEYWORDS

drug penetration
lascufloxacin
quinolones

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