Linked Life Data

10825468

Source:http://linkedlifedata.com/resource/pubmed/id/10825468

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-6-21
pubmed:abstractText
ATPase transporter proteins are commonly found in the hepatocyte canalicular membrane. Some of these, in particular the multidrug resistance (mdr1b) gene, have been previously demonstrated to be inducible genes. In this study, we found that tamoxifen induced expression of the mdr1b gene in the liver up to 40-fold after 14 days' exposure to tamoxifen in the diet at a concentration of 420 ppm. As tamoxifen and its metabolites are primarily excreted into the bile, we investigated if the increased expression of mdr1b in the liver following tamoxifen exposure had any effect on its excretion in rats. We found that the excretion of tamoxifen and its metabolites into bile was increased from 8 +/- 1% to 51 +/- 18% (mean +/- SD) of an administered dose of 180 nmol/kg over a collection period of 3 hr in rats that had received tamoxifen (35 mg/kg) orally for 12 days (plus a 3-day rest) prior to the experiment. These data suggest that prolonged treatment with tamoxifen may result in lower serum and tumour concentrations, due to a self-mediated enhancement of excretion via mdr1b gene-encoded P-glycoprotein. This may have implications for other drugs sharing the same route of excretion and co-administered with tamoxifen.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
233-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Association of tamoxifen biliary excretion rate with prior tamoxifen exposure and increased mdr1b expression.
pubmed:affiliation
MRC Toxicology Unit, University of Leicester, Hodgkin Building, P.O. Box 138, Lancaster Road, LE1 9HN, Leicester, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't