Linked Life Data

10958591

Source:http://linkedlifedata.com/resource/pubmed/id/10958591

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-12-13
pubmed:abstractText
There is an increasing interest to administer cytotoxic drugs to patients by the oral route. Quality of life issues, treatment advantages and pharmaco-economics are major arguments in favor of oral therapy. However, low or moderate bioavailability in combination with considerable interpatient variability are frequently observed which may reduce the feasibility of the oral route for this class of drugs with a generally narrow therapeutic window. Until recently, investigators focused on absorption enhancers which slightly damage the intestinal surface such as salicylates, methylxanthines and surfactants to improve the oral bioavailability of drugs. To date, a shift can be seen towards more subtle mechanisms to enhance the absorption. This review article focuses on two important mechanisms that determine the oral bioavailability of cytotoxic drugs. These include the presence of drug transporters in the intestinal epithelium pumping drugs into the intestinal lumen, such as MDR1 type P-glycoproteins, and first-pass elimination by cytochrome P450 isoenzymes (e.g. 3A4 and 3A5) or other enzymes in the intestines and/or liver. Currently preclinical and clinical studies are being performed to explore the feasibility of blocking these transporters/enzymes in order to achieve higher and less variable systemic drug levels after oral dosing. This review gives an update of the results of these studies. It is concluded however, that further research to unravel the processes involved in oral drug uptake is warranted to make the oral route a more efficient and consistent way of drug administration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0167-6997
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
231-41
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
The oral route for the administration of cytotoxic drugs: strategies to increase the efficiency and consistency of drug delivery.
pubmed:affiliation
Department of Clinical Chemistry, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't