Linked Life Data

1673419

Source:http://linkedlifedata.com/resource/pubmed/id/1673419

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1991-5-30
pubmed:abstractText
The metabolism of tamoxifen was examined in the rat, mouse, and human breast cancer patient. Large oral doses of tamoxifen (200 mg/kg) in the immature ovariectomized rat and mature mouse produced circulating levels of the parent compound, N-desmethyltamoxifen, and 4-hydroxytamoxifen quantifiable by HPLC separation, UV activation, and fluorescence detection. N-Desmethyltamoxifen and 4-hydroxytamoxifen serum levels in the mature ovariectomized mouse paralleled tamoxifen levels throughout a 96-hr time course after a single dose of tamoxifen. On the other hand, N-desmethyltamoxifen was the predominant serum metabolite after an equivalent dose of tamoxifen to the immature rat, but there was little 4-hydroxytamoxifen. Peak levels of tamoxifen occurred 3-6 hr after oral administration of tamoxifen in both species, whereas peak levels of N-desmethyltamoxifen in the immature rat did not occur until 24-48 hr. AUCs for tamoxifen and N-desmethyltamoxifen were approximately 4 times greater in the rat (57.5 and 111 micrograms.hr/ml, respectively) than the mouse (15.9 and 26.3 micrograms.hr/ml, respectively) after equivalent doses of tamoxifen (200 mg/kg). AUC of 4-hydroxytamoxifen for the rat (8.9 micrograms.hr/ml), however, was similar to that for the mouse (13.9 micrograms.hr/ml). The rate of elimination from serum was similar for tamoxifen, N-desmethyltamoxifen, and 4-hydroxytamoxifen in both the rat (t1/2 = 10.3, 12.1, and 17.2 hr, respectively) and the mouse (t1/2 = 11.9, 9.6, and 6 hr, respectively). Administration of large oral doses of tamoxifen (200 mg/kg) every 24 hr to mature ovariectomized mice or immature ovariectomized rats resulted in accumulation for the first 4 days.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
36-43
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:articleTitle
Metabolites, pharmacodynamics, and pharmacokinetics of tamoxifen in rats and mice compared to the breast cancer patient.
pubmed:affiliation
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't