Linked Life Data

16384676

Source:http://linkedlifedata.com/resource/pubmed/id/16384676

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2006-1-24
pubmed:abstractText
The contributions of P-glycoprotein (P-gp) and CYP3A to the oral bioavailability (BA) of cyclosporin A (CyA) were separately evaluated by using wild-type and mdr1a/1b knockout mice treated with dexamethasone (DEX). Mice were treated with DEX (1 or 75 mg/kg/day, i.p.) daily for 7 days, and the blood concentrations of CyA were measured after an i.v. or p.o. dose of CyA (10mg/kg) at 1.5h after the last DEX treatment. The BA values of CyA in wild-type and mdr1a/1b knockout mice were similar, 0.25 and 0.287, respectively. As regards expression of mdr1a and CYP3A mRNAs, expression of mdr1a mRNA was weakest in the duodenum, the main absorption site of CyA, along the whole intestine of wild-type mice, while expression of CYP3A was strongest in the duodenum of both types of mice. After treatment with 1 and 75 mg/kg DEX, the BA values decreased to 43 and 25% of the control in wild-type mice, respectively, and to 89 and 73% of the control in mdr1a/1b knockout mice, respectively. Expression of mdr1a mRNA in duodenum of wild-type mice was potently induced by DEX treatment. The expression of CYP3A mRNA in liver and duodenum of both strains was enhanced only by high-DEX treatment. These results suggest that P-glycoprotein plays only a small role in the absorption of CyA under physiological conditions, but the protein is readily induced by DEX and then functions as a more substantial absorption barrier to CyA than does CYP3A in the intestine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0378-5173
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
309
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
81-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16384676-ATP-Binding Cassette Transporters, pubmed-meshheading:16384676-Administration, Oral, pubmed-meshheading:16384676-Animals, pubmed-meshheading:16384676-Biological Availability, pubmed-meshheading:16384676-Cyclosporine, pubmed-meshheading:16384676-Cytochrome P-450 Enzyme System, pubmed-meshheading:16384676-Dexamethasone, pubmed-meshheading:16384676-Dose-Response Relationship, Drug, pubmed-meshheading:16384676-Immunosuppressive Agents, pubmed-meshheading:16384676-Injections, Intravenous, pubmed-meshheading:16384676-Intestinal Absorption, pubmed-meshheading:16384676-Intestine, Small, pubmed-meshheading:16384676-Liver, pubmed-meshheading:16384676-Male, pubmed-meshheading:16384676-Mice, pubmed-meshheading:16384676-Mice, Knockout, pubmed-meshheading:16384676-P-Glycoproteins, pubmed-meshheading:16384676-RNA, Messenger
pubmed:year
2006
pubmed:articleTitle
Contributions of intestinal P-glycoprotein and CYP3A to oral bioavailability of cyclosporin A in mice treated with or without dexamethasone.
pubmed:affiliation
Department of Clinical Pharmacy, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa 920-1192, Japan.
pubmed:publicationType
Journal Article, Comparative Study