Linked Life Data

10810389

Source:http://linkedlifedata.com/resource/pubmed/id/10810389

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2A
pubmed:dateCreated
2000-6-1
pubmed:abstractText
The intestinal transport properties and kinetics of camptothecin (CPT) through Caco-2 cell monolayers were characterized by determining concentration-, temperature-, and ATP-dependence as well as the effect of selected inhibitors. The absorptive permeability (Peff) of CPT was found to be concentration dependent and saturable (K(m) = 31.2 +/- 6.9 microM) indicating the involvement of a high affinity, low capacity transport system. CPT transport was also temperature dependent and inhibited by sodium azide plus 2-deoxyglucose, which deplete cellular ATP, further suggesting that an active, carrier-mediated transport system contributes to CPT absorption. Based on inhibition studies, the involvement of organic anion and cation transporters was implicated but not conclusively demonstrated. Total CPT transport decreased four fold with increasing pH from 5.5 to 8.5 indicating that CPT lactone contributed more significantly to overall CPT transport than CPT carboxylate. The results of these studies suggest that CPT absorption is mediated by multiple mechanisms including significant passive diffusion and active transport components. Since typical substrates for intestinal carriers are hydrophilic and charged, the involvement of putative absorptive carriers in the transport of CPT is a novel finding that may give insight into the erratic oral bioavailability of CPTs observed in the clinic.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0250-7005
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1013-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:articleTitle
The intestinal absorption of camptothecin, a highly lipophilic drug, across Caco-2 cells is mediated by active transporter(s).
pubmed:affiliation
Cancer Institute of New Jersey, New Brunswick 08901, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't