Linked Life Data

19239981

Source:http://linkedlifedata.com/resource/pubmed/id/19239981

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2009-4-24
pubmed:abstractText
P-glycoprotein (P-gp) is a transporter that mediates the tissue disposition of numerous drugs. To evaluate the role of P-glycoprotein (P-gp) in aripiprazole tissue distribution and penetration across the blood-brain barrier, mice deficient in the P-gp gene (Abcb1a/b-/-) were dosed intraperitoneally with 2 microg/g mouse of the antipsychotic drug aripiprazole. Wildtype FVB mice were administered the same dose as transgenic animals. At one, two, and three hours after dosing, blood and tissue samples were collected and assayed for aripiprazole concentration by HPLC. Deficiency of P-gp did not result in significantly altered plasma drug concentrations but had dramatic effects on drug concentrations in brain tissue. At 1, 2, and 3 h after dosing, aripiprazole brain concentrations in the Abcb1a/b-/- mice were 4.6-, 4.1- and 3.0-fold higher, respectively (P<0.01), compared with the wildtype mice. Increases in drug concentration were also observed in testes and muscle in Abcb1a/b -/- mice. All other tissues including gut, lung, heart, kidney, liver, and spleen did not show significant differences between the two groups. These data provide evidence that aripiprazole is a transportable substrate of P-gp. Thus, factors influencing P-gp activity within the blood brain barrier in humans may have implications for the therapeutic effects and tolerability of aripiprazole.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0920-9964
pubmed:author
pubmed:issnType
Print
pubmed:volume
110
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
90-4
pubmed:dateRevised
2010-9-2
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Aripiprazole brain concentration is altered in P-glycoprotein deficient mice.
pubmed:affiliation
Laboratory of Drug Disposition and Pharmacogenetics, Department of Psychiatry, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural