Linked Life Data

14744620

Source:http://linkedlifedata.com/resource/pubmed/id/14744620

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2004-1-27
pubmed:abstractText
The present study aims to investigate whether azithromycin reverses P-glycoprotein-dependent anticancer drug resistance in vitro and modifies the hepatobiliary excretion of doxorubicin, a substrate for P-glycoprotein in vivo. Azithromycin increased dose-dependently the intracellular accumulation of doxorubicin in adriamycin-resistant human myelogenous leukemia cells (K562/ADR) with no effect on the expression of P-glycoprotein in the cells. However, the inhibitory effect was much weaker than that of cyclosporin A and was comparable to that of erythromycin. When Sprague-Dawley (SD) rats, which have drug transporting P-glycoprotein and multidrug resistance-associated protein 2 (Mrp2) in the bile canalicular membrane of hepatocytes, received an infusion of doxorubicin, the steady-state biliary clearance of doxorubicin was significantly decreased for 40 min after a single intravenous injection of azithromycin. However, azithromycin did not increase the plasma concentration of doxorubicin. The biliary clearance of doxorubicin in Eisai hyperbilirubinemic rats (EHBRs), which have a hereditary deficiency in Mrp2, was significantly decreased compared with that in Sprague-Dawley rats, suggesting the involvement of Mrp2 in the biliary excretion of doxorubicin. The present findings suggest that azithromycin overcomes P-glycoprotein-dependent anticancer drug resistance of tumors by inhibiting the binding of doxorubicin to P-glycoprotein in K562/ADR cells and inhibits the hepatobiliary excretion of drugs that are substrates for P-glycoprotein and Mrp2.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
484
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
333-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Azithromycin reverses anticancer drug resistance and modifies hepatobiliary excretion of doxorubicin in rats.
pubmed:affiliation
Department of Medical Technology, Nagoya University School of Health Sciences, 1-1-20 Daikominami, Higashi, Nagoya 461-8673, Japan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't