Document Detail

Uptake and intracellular activity of ketolide HMR 3647 in human phagocytic and non-phagocytic cells.
MedLine Citation:
PMID:  11298144     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To evaluate the uptake of HMR 3647 into human neutrophils (PMNs), human peritoneal macrophages (PMOs) and tissue-cultured cells (epithelial cells and fibroblasts), and to assess the intracellular activity of this drug. METHOD: Cell uptake of HMR 3647 was measured by radiometric assay, as described by Klemper and Styrt. Intracellular activity was determined by incubation for 3 h of PMNs containing bacteria in the presence of HMR 3647. RESULTS: The intracellular concentrations were 130 and 71 times higher than extracellular concentrations in PMNs and PMOs, respectively (extracellular concentrations: 2-25 mg/L). The cellular-to-extracellular concentration ratios (C/E) for tissue-cultured cells were lower than those obtained in phagocytic cells but still greater than 5. The uptake of HMR 3647 was rapid and non-saturable in all cells. HMR 3647 was released slowly from phagocytic cells. HMR 3647 (extracellular concentration: 0.5-10 mg/L) did not significantly reduce the intracellular survival rate of Staphylococcus aureus ATCC 25923 in PMNs. CONCLUSIONS: HMR 3647 reaches intracellular concentrations several times higher than extracellular concentrations within phagocytic and non-phagocytic cells. The slow efflux of this drug from phagocytic cells suggests that these cells may be a vehicle for it, delivering it to sites of infection.
Pascual A; S Ballesta; I García; E J Perea
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases     Volume:  7     ISSN:  1198-743X     ISO Abbreviation:  Clin. Microbiol. Infect.     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-04-12     Completed Date:  2001-08-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9516420     Medline TA:  Clin Microbiol Infect     Country:  France    
Other Details:
Languages:  eng     Pagination:  65-9     Citation Subset:  IM    
Department of Microbiology, School of Medicine, Sevilla, Spain.
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MeSH Terms
Anti-Bacterial Agents / pharmacokinetics*,  pharmacology
Cells, Cultured
Epithelial Cells / metabolism*
Fibroblasts / metabolism*
Macrophages, Peritoneal / metabolism
Neutrophils / metabolism,  microbiology
Phagocytes / metabolism*
Staphylococcal Infections / microbiology
Staphylococcus aureus / drug effects,  growth & development
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Ketolides; 0/Macrolides; 0/telithromycin

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