Journal
PHARMACOGENOMICS
Volume 11, Issue 10, Pages 1427-1438Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/PGS.10.126
Keywords
ABC transporter; antiepileptic drug; drug resistance; epilepsy; P-glycoprotein; polymorphism
Categories
Funding
- Deutsche Forschungsgemeinschaft [DFG PO681/4-1]
- European Community [201380]
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Drug resistance in epilepsy is considered a complex and multifactorial problem. Overexpression of efflux transporters at the blood brain barrier is discussed as one factor that might limit brain penetration and efficacy of antiepileptic drugs. Whereas experimental data render support for this hypothesis, there is still a lack of sufficient clinical evidence indicating a functional role of efflux transporters. Pharmacogenetic analysis has been considered as one approach in the evaluation of a putative link between transporters and drug-resistant epilepsy. However, the likelihood of a multifactorial nature of drug resistance and the complexity of the events regulating transporters pose a major challenge to any attempt at linking selected genetic polymorphisms to the outcome of drug therapy. In this article, the evidence for an impact of efflux transporters on the response to antiepileptic drugs is discussed, focusing in particular on the different issues presenting a challenge for pharmacogenetic approaches in this field.
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