Journal
NEUROREPORT
Volume 12, Issue 11, Pages 2387-2389Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00001756-200108080-00020
Keywords
antiepileptic drugs; epilepsy; multidrug transporter; pharmacoresistance
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The mechanisms that lead to drug resistance in epilepsy are not known. Recently, overexpression of multidrug transporters, such as multidrug resistance-associated protein (MRP), has been reported in surgically resected epileptogenic human brain tissue and suggested to contribute to the drug resistance of epilepsy. However, it is not known to what extent multidrug transporters such as MRP are involved in transport of antiepileptic drugs. In the present study, we used in vivo microdialysis in rats to study whether the concentration of phenytoin in the extracellular fluid of the cerebral cortex can be enhanced by inhibition of MRP, using the MRP inhibitor probenecid. Local perfusion with probenecid via the micro-dialysis probe significantly enhanced the extracellular concentration of phenytoin. The data indicate that MRP critically participates in the regulation of extracellular brain concentrations of the major antiepileptic drug phenytoin. NeuroReport 12:2387-2389 (C) 2001 Lippincott Williams & Wilkins.
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