Linked Life Data

12113905

Source:http://linkedlifedata.com/resource/pubmed/id/12113905

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-7-12
pubmed:abstractText
Although a series of new antiepileptic drugs (AEDs) have been launched in the last two decades, drug-refractoriness remains a major problem concerning 20-30% of epileptic patients. The fact that most patients with refractory epilepsy are resistant to several AEDs acting via different targets points to an involvement of unspecific mechanisms like changes in local uptake of AEDs in the epileptic focus region. Increased expression of multidrug transporters has been reported in epileptogenic brain tissue from pharmacoresistant patients undergoing epilepsy surgery. However, only limited information exists on the extent to which AEDs are transported by multidrug transporters like P-glycoprotein (PGP). In the present study, the effect of PGP inhibition by verapamil on brain access of the AEDs phenobarbital, lamotrigine, and felbamate was investigated by in vivo microdialysis in rats. Local perfusion of verapamil via the microdialysis probe increased the concentration of the three AEDs in the extracellular fluid of the cerebral cortex in a significant manner. The data indicate that overexpression of PGP in epileptic tissue is likely to limit brain access of the AEDs phenobarbital, lamotrigine, and felbamate, thus favoring the hypothesis that multidrug transporters play a crucial role in the phenomenon of drug-refractory epilepsy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0304-3940
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
327
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
173-6
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
P-Glycoprotein-mediated efflux of phenobarbital, lamotrigine, and felbamate at the blood-brain barrier: evidence from microdialysis experiments in rats.
pubmed:affiliation
Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Bünteweg 17, D-30559, Hannover, Germany. heidrun.potschka@tiho-hannover.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't