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Pharmacokinetics of telithromycin using bronchoscopic microsampling after single and multiple oral doses
|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|
|Epithelial lining fluid|
|Issue Date: ||Oct-2007|
|Publisher: ||Elsevier Ltd.|
|Journal Title: ||Pulmonary Pharmacology & Therapeutics|
|Start Page: ||549|
|End Page: ||555|
|Publisher DOI: ||10.1016/j.pupt.2006.05.006|
|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.|
|Type: ||article (author version)|
|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