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Pharmacokinetics of telithromycin using bronchoscopic microsampling after single and multiple oral doses

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Title: Pharmacokinetics of telithromycin using bronchoscopic microsampling after single and multiple oral doses
Authors: Kikuchi, Junko Browse this author
Yamazaki, Koichi Browse this author
Kikuchi, Eiki Browse this author
Ishizaka, Akitoshi Browse this author
Nishimura, Masaharu Browse this author →KAKEN DB
Keywords: Telithromycin
Bronchoscopic microsampling
Bronchoscopy
Antimicrobial agent
Pharmacokinetics
Epithelial lining fluid
Issue Date: Oct-2007
Publisher: Elsevier Ltd.
Journal Title: Pulmonary Pharmacology & Therapeutics
Volume: 20
Issue: 5
Start Page: 549
End Page: 555
Publisher DOI: 10.1016/j.pupt.2006.05.006
PMID: 17127087
Abstract: Objectives: Bronchoscopic microsampling (BMS) is a new technique for repeated sampling of bronchial epithelial lining fluid (ELF) to obtain the pharmacokinetic profile of drugs. We analyzed the time versus concentration profiles of telithromycin in bronchial ELF obtained by BMS and compared these finding to those in plasma and alveolar ELF obtained by bronchoalveolar lavage (BAL). Methods: Bronchial ELF samples were obtained from five healthy subjects using BMS probe at 0, 2, 3, 4, 6, 10 and 24 h after single or multiple oral doses of 600 mg of telithromycin. Alveolar ELF was also obtained by BAL 3 h after single or multiple oral doses of 600 mg of telithromycin. Results: The areas under the concentration–time curve from 0 to 24 h (AUC0-24) of telithromycin in plasma and bronchial ELF were 2.86±0.60 and 19.5±10.4 mg h/l after single treatment and 3.60±0.49 and 42.2±22.7 mg h/l after multiple treatments, respectively. Single and multiple oral doses of telithromycin produced significantly (p<0.05) higher AUC0-24 in bronchial ELF compared to those in plasma. While concentrations in bronchial ELF obtained by BMS were significantly lower than those in alveolar ELF obtained by BAL, they tended to be higher than those in plasma after multiple administration. The telithromycin concentrations obtained by BMS method were very consistent in bronchial ELF at different bronchi at one time point and at the same bronchus at different time points. Conclusions: Using the BMS technique, we could describe the pharmacokinetics of telithromycin in bronchial ELF. Furthermore, BMS was reasonably validated and reconfirmed to be a feasible and reliable method for measuring antimicrobial concentrations in bronchial ELF.
Relation: http://www.sciencedirect.com/science/journal/10945539
Type: article (author version)
URI: http://hdl.handle.net/2115/30118
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 山崎 浩一

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