Linked Life Data

17446265

Source:http://linkedlifedata.com/resource/pubmed/id/17446265

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-6-20
pubmed:abstractText
Recently, breast cancer resistance protein (BCRP/ABCG2) has been shown to limit the oral absorption of its substrates in the intestine. The purpose of this study was to examine whether excipients can be used as inhibitors of BCRP, to improve the oral drug absorption of BCRP substrates. In wild-type mice, Pluronic P85 and Tween 20, given orally 15 min before topotecan administration, increased the area under the plasma concentration-time curve (AUC) of topotecan after oral administration (2.0- and 1.8-fold, respectively). In contrast, Pluronic P85 and Tween 20 were less effective (no significant difference) on the AUC of topotecan after oral administration in Bcrp (-/-) mice (1.2- and 1.2-fold, respectively). Pluronic P85 and Tween 20 given orally did not affect significantly the AUC of topotecan after intravenous administration in wild-type and Bcrp (-/-) mice. Moreover, we determined the mucosal-to-serosal absorptive transport of topotecan using everted mouse ileum. Pluronic P85 and Tween 20 significantly increased the intestinal absorption rate of topotecan in everted sacs from wild-type mice whereas, in everted sacs from Bcrp (-/-) mice, the absorption rate was 2.1-fold greater than that in wild-type mice, and these excipients were not significantly effective. There was no significant difference in the intestinal P-glycoprotein (P-gp) expression and serosal-to-mucosal secretory transport of rhodamine 123, a typical P-gp substrate. Taken together, these results suggest that Pluronic P85 and Tween 20 can improve the oral bioavailability of BCRP substrates by inhibiting BCRP function in the small intestine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1142-8
pubmed:meshHeading
pubmed-meshheading:17446265-ATP-Binding Cassette Transporters, pubmed-meshheading:17446265-Administration, Oral, pubmed-meshheading:17446265-Animals, pubmed-meshheading:17446265-Antineoplastic Agents, pubmed-meshheading:17446265-Area Under Curve, pubmed-meshheading:17446265-Biological Availability, pubmed-meshheading:17446265-Dose-Response Relationship, Drug, pubmed-meshheading:17446265-Excipients, pubmed-meshheading:17446265-Female, pubmed-meshheading:17446265-Injections, Intravenous, pubmed-meshheading:17446265-Intestinal Absorption, pubmed-meshheading:17446265-Intestines, pubmed-meshheading:17446265-Mice, pubmed-meshheading:17446265-Mice, Knockout, pubmed-meshheading:17446265-P-Glycoprotein, pubmed-meshheading:17446265-Poloxalene, pubmed-meshheading:17446265-Polysorbates, pubmed-meshheading:17446265-Topotecan
pubmed:year
2007
pubmed:articleTitle
Improvement of the oral drug absorption of topotecan through the inhibition of intestinal xenobiotic efflux transporter, breast cancer resistance protein, by excipients.
pubmed:affiliation
Department of Pharmaceutics, Hoshi University, Shinagawa, Tokyo 142-8501, Japan.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't