Linked Life Data

21071521

Source:http://linkedlifedata.com/resource/pubmed/id/21071521

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-19
pubmed:abstractText
Apixaban, a potent and highly selective factor Xa inhibitor, is currently under development for treatment of arterial and venous thrombotic diseases. The distribution, metabolism, and elimination of [(14)C]apixaban were investigated in male, female, pregnant, and lactating rats after single oral doses. Tissue distribution of radioactivity in rats was measured using quantitative whole-body autoradiography. After a single oral administration, radioactivity distributed quickly in rats with C(max) at 1 h for most tissues. The elimination t(1/2) of radioactivity in blood was 1.7 to 4.2 h. The blood area under the plasma concentration-time curve of radioactivity was similar between male and female rats and was slightly higher in pregnant rats and lower in lactating rats. The radioactivity concentration in tissues involved in elimination was greater than that in blood with the highest concentration in the gastrointestinal tract, liver, and urinary bladder/contents and lowest level in brains. In pregnant rats, the whole-body autoradiogram showed that low levels of radioactivity were present in fetal blood, liver, and kidney and were much lower than the radioactivity in the respective maternal organs. The fecal route was the major pathway (74% of dose), and the urinary route was the minor pathway (14%) for apixaban elimination. After single oral doses of [(14)C]apixaban to lactating rats, apixaban exhibited extensive lacteal excretion with apixaban as the major component. In summary, tissue distribution of apixaban in rats was extensive but with limited transfer to fetal and brain tissues and extensive secretion into rat milk with the parent drug as the major component. Milk excretion could account for 10% of apixaban dose, which was comparable to urinary elimination in rats. Tissue distribution and drug excretion of apixaban are consistent with those for a moderately permeable drug that is a substrate for P-glycoprotein and breast cancer resistance protein efflux transporters.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1521-009X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
256-64
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Tissue distribution and elimination of [14C]apixaban in rats.
pubmed:affiliation
Pharmaceutical Candidate Optimization , Bristol-Myers Squibb, P.O. Box 4000, Princeton, NJ 08543, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't