Document Detail

Differences in assessment of macrolide interaction with human MDR1 (ABCB1, P-gp) using rhodamine-123 efflux, ATPase activity and cellular accumulation assays.
MedLine Citation:
PMID:  20621639     Owner:  NLM     Status:  MEDLINE    
In this study five macrolide antibiotics (azithromycin, erythromycin, clarithromycin, roxithromycin and telithromycin) were compared based on their ability to interact with human MDR1 (ABCB1, P-glycoprotein), studied from two main aspects: by determining the influence of macrolide antibiotics on MDR1 function, as well as the influence of MDR1 on macrolide accumulation in MES-SA/Dx5 cells overexpressing human MDR1. At higher micromolar concentrations five tested macrolides were shown to inhibit MDR1 function in terms of rhodamine-123 efflux and verapamil-activated ATPase function, whereas at lower concentrations they activated MDR1 ATPase. They were confirmed to be substrates of MDR1 and to compete with each other, as well as with verapamil for transport via this transporter. Expression of MDR1 on cells decreased macrolide accumulation in cells from 2- to 80-fold with the most pronounced change observed for azithromycin and erythromycin. Moreover, presence of active MDR1 highly affected the relative ranking of tested macrolides according to their accumulation in cells. In conclusion, out of seven applied methods and assessed parameters, four of them gave similar rough evaluation on the strength of interaction of five macrolides with MDR1, with clarithromycin, roxithromycin and telithromycin showing stronger interaction than azithromycin and erythromycin.
Vesna Munić; Zeljko Kelnerić; Lara Mikac; Vesna Eraković Haber
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Publication Detail:
Type:  Journal Article     Date:  2010-06-08
Journal Detail:
Title:  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences     Volume:  41     ISSN:  1879-0720     ISO Abbreviation:  Eur J Pharm Sci     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-07-19     Completed Date:  2010-11-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9317982     Medline TA:  Eur J Pharm Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  86-95     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier B.V. All rights reserved.
GlaxoSmithKline Research Centre Zagreb Ltd, Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia.
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MeSH Terms
Adenosine Triphosphatases / metabolism*
Base Sequence
Blotting, Western
DNA Primers
Flow Cytometry
Macrolides / chemistry*
P-Glycoprotein / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Rhodamine 123 / metabolism*
Reg. No./Substance:
0/DNA Primers; 0/Macrolides; 0/P-Glycoprotein; 62669-70-9/Rhodamine 123; EC 3.6.1.-/Adenosine Triphosphatases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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