Linked Life Data

19491029

Source:http://linkedlifedata.com/resource/pubmed/id/19491029

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3-4
pubmed:dateCreated
2009-6-3
pubmed:abstractText
Carriers may mediate the permeation across enterocytes for drug substances being organic anions. Carrier mediated permeation for the organic anions estrone-3-sulfate (ES) and glipizide across Caco-2 cells were investigated kinetically, and interactions on involved carriers evaluated. Initial uptakes (P(UP)) at apical and basolateral membranes, apparent permeabilities (P(APP)) and corresponding intracellular end-point accumulations (P(EPA)) of radioactive labeled compounds were studied. Possible effects of other anionic compounds were investigated. Apical P(UP) and absorptive P(APP) for ES were inhibited and its absorptive P(EPA) prevented in presence of the investigated organic anions and apical P(UP) was saturable with K(m) 23microM. Basolateral P(UP) and exsorptive P(APP) were inhibited, its exsorptive P(EPA) was prevented, and basolateral P(UP) and exsorptive P(APP) were saturable with K(m) 44microM and 38microM, respectively. BCRP inhibition affected both absorptive an exsorptive P(EPA) and P(APP) for ES. Glipizide apical P(UP) and absorptive P(APP) were not inhibitable. Basolateral P(UP) for glipizide was inhibitable, its P(EPA) prevented, and P(UP) was saturable with K(m) 56microM, but exsorptive P(APP) was not affected. Carrier mediated exsorption kinetics for ES are seen at both apical and basolateral membranes, resulting in predominant exsorption despite presence of absorptive carrier(s). Carrier mediated basolateral P(UP) for glipizide was observed, but glipizide P(APP) was not described by carrier kinetics. However, glipizide is affecting exsorption for ES, due to interactions on basolateral carrier. The study confirms that estrone-3-sulfate can be used to characterize anionic carrier kinetics. Furthermore it is suggested that estrone-3-sulfate may be used to identify compounds which may interact on anionic carriers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1879-0720
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
378-86
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Impact of carriers in oral absorption: Permeation across Caco-2 cells for the organic anions estrone-3-sulfate and glipizide.
pubmed:affiliation
Molecular Biopharmaceutics, Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't