Document Detail


Transport characteristics of clarithromycin, azithromycin and telithromycin, antibiotics applied for treatment of respiratory infections, in Calu-3 cell monolayers as model lung epithelial cells.
MedLine Citation:
PMID:  22764569     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
We have shown that clarithromycin (CAM), a macrolide antibiotic, more highly distributes from plasma to lung epithelium lining fluid (ELF), the infection site of pathogens, than azithromycin (AZM) and telithromycin (TEL). Transporter(s) expressed on lung epithelial cells may contribute to the distribution of the compiunds to the ELF. However, distribution mechanisms are not well known. In this study, their transport characteristics in Calu-3 cell monolayers as model lung epithelial cells were examined. The basolateral-to-apical transport of CAM through Calu-3 cell monolayers was greater than that of AZM and TEL. Although verapamil and cyclosporine A as MDR1 substrates completely inhibited the basolateral-to-apical transport, probenecid as MRP1 inhibitor did not show an effect. These results suggest that the antibiotics are transported from plasma to ELF by MDR1 of lung epithelial cells. In addition, their affinity and binding rate to MDR1 was examined by ATP activity assay. The affinity and binding rate of CAM was greater than those of AZM and TEL. These corresponded with the distributions from plasma to ELF as described above. The present study suggests that the more highly distribution of CAM from plasma to ELF is due to the high affinity and binding rate to MDR1 of lung epithelial cells.
Authors:
K Togami; S Chono; K Morimoto
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Die Pharmazie     Volume:  67     ISSN:  0031-7144     ISO Abbreviation:  Pharmazie     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-07-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9800766     Medline TA:  Pharmazie     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  389-93     Citation Subset:  IM    
Affiliation:
Department of Clinical Pharmacy, School of Pharmaceutical Science, Ohu University, Fukushima, Japan.
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