Abstract：
:Epilepsy is the most common serious chronic neurological disorder. Current data show that one-third of patients do not respond to anti-epileptic drugs (AEDs). Most non-responsive epilepsy patients are resistant to several, often all, AEDs, even though the drugs differ from each other in pharmacokinetics, mechanisms of action, and interaction potential. The mechanisms underlying drug resistance of epilepsy patients are still not clear. In recent years, one of the potential mechanisms interesting researchers is over-expression of P-glycoprotein (P-gp, also known as ABCB1 or MDR1) in endothelial cells of the blood-brain barrier (BBB) in epilepsy patients. P-gp plays a central role in drug absorption and distribution in many organisms. The expression of P-gp is greater in drug-resistant than in drug-responsive patients. Some studies also indicate that several AEDs are substrates or inhibitors of P-gp, implying that P-gp may play an important role in drug resistance in refractory epilepsy. In this article, we review the clinical and laboratory evidence that P-gp expression is increased in epileptic brain tissues and that AEDs are substrates of P-gp in vitro and in vivo. We discuss criteria for identifying the substrate status of AEDs and use structure-activity relationship (SAR) models to predict which AEDs act as P-gp substrates.
journal_name
Adv Drug Deliv Revjournal_title
Advanced drug delivery reviewsauthors
Zhang C,Kwan P,Zuo Z,Baum Ldoi
10.1016/j.addr.2011.12.003subject
Has Abstractpub_date
2012-07-01 00:00:00pages
930-42issue
10eissn
0169-409Xissn
1872-8294pii
S0169-409X(11)00297-3journal_volume
64pub_type
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journal_title：Advanced drug delivery reviews
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journal_title：Advanced drug delivery reviews
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doi：10.1016/j.addr.2006.09.011
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