| pubmed-article:12604685 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12604685 | lifeskim:mentions | umls-concept:C0006104 | lld:lifeskim |
| pubmed-article:12604685 | lifeskim:mentions | umls-concept:C1704711 | lld:lifeskim |
| pubmed-article:12604685 | lifeskim:mentions | umls-concept:C1549479 | lld:lifeskim |
| pubmed-article:12604685 | lifeskim:mentions | umls-concept:C0906802 | lld:lifeskim |
| pubmed-article:12604685 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:12604685 | pubmed:dateCreated | 2003-2-26 | lld:pubmed |
| pubmed-article:12604685 | pubmed:abstractText | The adequate distribution of STI-571 (Gleevec) to the central nervous system (CNS) is critical for its effective use in CNS tumors. P-glycoprotein-mediated efflux in the blood-brain barrier may play a role in the CNS delivery of this drug. Whether STI-571 is a substrate of P-glycoprotein was determined by examining the directional flux of [(14)C]STI-571 in parental and MDR1-transfected Madin-Darby canine kidney (MDCK) II epithelial cell monolayers. The basolateral-to-apical flux of STI-571 was 39-fold greater than the apical-to-basolateral flux in the MDR1-transfected cells and 8-fold greater in the parental cell monolayers. This difference in directional flux was significantly reduced by a specific P-glycoprotein inhibitor (2R)-anti-5-[3-[4-(10,11-difluoromethanodibenzo-suber-5-yl)piperazin-1-yl]-2-hydroxypropoxy]quinoline trihydrochloride (LY335979). The role of P-glycoprotein in the CNS distribution of STI-571 was examined in vivo, using wild-type and mdr1a/b (-/-) knockout mice that were orally administered 25 mg/kg [(14)C]STI-571. In the wild-type mice, the brain-to-plasma STI-571 concentration ratio at all time points was low (1-3%); however, there was an 11-fold greater brain partitioning of STI-571 at 1 h postdose in the mdr1a/b (-/-) mice compared with the wild-type mice. When 12.5 mg/kg STI-571 was given intravenously, the brain-to-plasma ratio of STI-571 in the mdr1a/b (-/-) mice was approximately 7-fold greater than that of wild-type mice up to 120 min postdose. These data indicate that STI-571 is a substrate of P-glycoprotein, and that the inhibition of P-glycoprotein affects the transport of STI-571 across MDCKII monolayers. Moreover, P-glycoprotein plays an important role in limiting the distribution of STI-571 to the CNS. | lld:pubmed |
| pubmed-article:12604685 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12604685 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12604685 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12604685 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:12604685 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12604685 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12604685 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:12604685 | pubmed:issn | 0022-3565 | lld:pubmed |
| pubmed-article:12604685 | pubmed:author | pubmed-author:HayesMichaelM | lld:pubmed |
| pubmed-article:12604685 | pubmed:author | pubmed-author:LemaireMichel... | lld:pubmed |
| pubmed-article:12604685 | pubmed:author | pubmed-author:MarbachPeterP | lld:pubmed |
| pubmed-article:12604685 | pubmed:author | pubmed-author:ElmquistWilli... | lld:pubmed |
| pubmed-article:12604685 | pubmed:author | pubmed-author:DaiHaiQingH | lld:pubmed |
| pubmed-article:12604685 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12604685 | pubmed:volume | 304 | lld:pubmed |
| pubmed-article:12604685 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12604685 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12604685 | pubmed:pagination | 1085-92 | lld:pubmed |
| pubmed-article:12604685 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
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| pubmed-article:12604685 | pubmed:meshHeading | pubmed-meshheading:12604685... | lld:pubmed |
| pubmed-article:12604685 | pubmed:year | 2003 | lld:pubmed |
| pubmed-article:12604685 | pubmed:articleTitle | Distribution of STI-571 to the brain is limited by P-glycoprotein-mediated efflux. | lld:pubmed |
| pubmed-article:12604685 | pubmed:affiliation | Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455, USA. | lld:pubmed |
| pubmed-article:12604685 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12604685 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:12604685 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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