Lack of interactions between breast cancer resistance protein (bcrp/abcg2) and selected antiepileptic agents
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16529607
DOI
10.1111/j.1528-1167.2006.00453.x
PII: EPI453
Knihovny.cz E-resources
- MeSH
- ATP Binding Cassette Transporter, Subfamily G, Member 2 MeSH
- ATP-Binding Cassette Transporters antagonists & inhibitors metabolism pharmacokinetics MeSH
- Anticonvulsants pharmacokinetics pharmacology therapeutic use MeSH
- Biological Availability MeSH
- Endothelial Cells drug effects metabolism MeSH
- Epilepsy drug therapy metabolism MeSH
- Blood-Brain Barrier drug effects metabolism MeSH
- Capillary Permeability drug effects MeSH
- Cells, Cultured MeSH
- Drug Interactions MeSH
- Humans MeSH
- Drug Resistance, Multiple drug effects MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Neoplasm Proteins antagonists & inhibitors metabolism pharmacokinetics MeSH
- In Vitro Techniques MeSH
- Transfection MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ATP Binding Cassette Transporter, Subfamily G, Member 2 MeSH
- ATP-Binding Cassette Transporters MeSH
- ABCG2 protein, human MeSH Browser
- Anticonvulsants MeSH
- Neoplasm Proteins MeSH
PURPOSE: Recent studies have indicated constitutive expression of efflux transporter, breast cancer resistance protein (BCRP, ABCG2), in endothelial cells of the blood-brain barrier (BBB). In epileptogenic brain tumors such as ganglioma, astrocytoma, anaplastic astrocytomas, or glioma multiforme, strong expression of BCRP in the microvasculature of the BBB was observed. Therefore it was hypothesized that this phenomenon could critically influence the bioavailability of drugs in these tumors and potentially contribute to the failure of antiepileptic treatment. The aim of this study was to test whether some commonly used antiepileptic drugs (AEDs) are substrates transported by human BCRP. In particular, we focused on phenobarbital, phenytoin, ethosuximide, primidone, valproate, carbamazepine, clonazepam, and lamotrigine. Furthermore, the inhibitory potency of these AEDs to BCRP was examined. METHODS: To study substrate affinity of tested AEDs to BCRP, transport experiments were performed in epithelial BCRP-expressing MDCKII-BCRP and MDCKII-parent cell lines cultured on microporous membrane. For detection of inhibitory potency of AEDs to BCRP, accumulation assays were carried out in MEF3.8-BCRP cells with known BCRP substrates, BODIPY FL prazosin and mitoxantrone. RESULTS: No obvious interactions of tested AEDs with BCRP transporter were observed. Therefore these drugs in relevant therapeutic concentrations are neither substrates nor inhibitors of BCRP. CONCLUSIONS: Based on our in vitro data we can conclude that resistance to treatment with the tested AEDs probably is not caused by the overexpression of BCRP in the BBB of epileptogenic brain tumors.
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