Linked Life Data

15876414

Source:http://linkedlifedata.com/resource/pubmed/id/15876414

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-5-6
pubmed:abstractText
Tamoxifen is the most used anticancer drug and is approved for chemoprevention. Little is known about the enzyme inducing properties of low-dose regimens and the influence of route of administration. In this study, nude rats received 5 mg/kg/day of tamoxifen orally or a 50 mg continuous-release pellet subcutaneously. The mRNAs for cytochrome P450-enzymes (CYPs), flavin-containing monooxygenase 1 (FMO1) and phase II drug-metabolising enzymes were quantified by real-time RT-PCR. Tamoxifen and metabolite concentrations were measured using HPLC. We observed a significant increase in CYP3A18 and FMO1 mRNA expression levels in the orally treated animals, whereas the increase in CYP3A2 expression did not reach statistical significance (p=0.057). No significant induction of enzyme expression was observed in rats that received subcutaneous (S.c.) treatment. After 33 days the serum levels of 4-hydroxytamoxifen (4OHtam), tamoxifen and N-desmethyltamoxifen (NDtam) in orally treated animals were 1.8+/-0.7, 11.1+/-3.2 and 11.4+/-3.8 ng/ml, respectively. In subcutaneously treated animals, tamoxifen and N-desmethyltamoxifen were detected in tissues, but not in serum. These data demonstrate that in contrast to the subcutaneous administration, low-dose oral tamoxifen induced tamoxifen-metabolising enzymes. Furthermore, the different routes of administration resulted in different serum and tissue levels of tamoxifen and metabolites.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0960-0760
pubmed:author
pubmed:issnType
Print
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
489-98
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Induction of hepatic drug-metabolising enzymes and tamoxifen metabolite profile in relation to administration route during low-dose treatment in nude rats.
pubmed:affiliation
Section for Endocrinology, Institute of Medicine, University of Bergen, Norway.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't