Linked Life Data

10518631

Source:http://linkedlifedata.com/resource/pubmed/id/10518631

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1999-12-22
pubmed:abstractText
Cytochrome P-450 3A4 (CYP3A4), the major phase I drug metabolizing enzyme in humans, and the multidrug efflux pump, MDR or P-glycoprotein (P-gp), are present at high levels in the villus tip enterocytes of the small intestine, the primary site of absorption for orally administered drugs. These proteins are induced or inhibited by many of the same compounds and demonstrate a broad overlap in substrate and inhibitor specificities, suggesting that they act as a concerted barrier to drug absorption. A series of studies from our laboratory of cyclosporine and tacrolimus in humans and a novel cysteine protease inhibitor in rats, dosed concomitantly with inhibitors and inducers of CYP3A4 and P-gp, suggest that gut extraction can be modeled using measures of intestinal metabolism and absorption rate, the latter reflecting changes in P-gp. Results evaluating a preliminary model applied to the CYP3A substrate drugs midazolam, indinavir, saquinavir, and rifabutin suggest that the model may be useful for predicting in vivo intestinal metabolism from in vitro data.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0168-3659
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25-31
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Intestinal MDR transport proteins and P-450 enzymes as barriers to oral drug delivery.
pubmed:affiliation
Department of Biopharmaceutical Sciences, University of California, San Francisco, CA 94143-0446, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.