Journal article

Exploring the possible interaction between anti-epilepsy drugs and multidrug efflux pumps; in vitro observations

Francesca Rivers, Terence J O'Brien, Richard Callaghan

EUROPEAN JOURNAL OF PHARMACOLOGY | ELSEVIER SCIENCE BV | Published : 2008

Abstract

Approximately one-third of patients with epilepsy display an inherent resistance to pharmacological therapy, manifest as continuing seizures despite maximal tolerated doses of anti-epileptic drugs. One hypothesis for the underlying mechanism of anti-epileptic drug pharmacoresistance is lower drug entry to the epileptic neurones due to the activity of multidrug efflux pumps from the ATP Binding Cassette (ABC) superfamily at the blood-brain barrier. There has been a steady accumulation of animal and human data supporting this theory, particularly for ABC(B1) (P-glycoprotein). However, much of this evidence is indirect. In the present study, several anti-epileptic drugs (carbamazepine, valproic..

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Grants

Awarded by Cancer Research UK Program


Funding Acknowledgements

The authors kindly acknowledge the provision of the COR/L23<SUP>Adr</SUP> and MCF7/FLV<SUP>1000</SUP> cell lines by Prof M Barrand (Cambridge University) and Prof S Bates (NCI, USA) respectively. The research was supported by a Cancer Research UK Program Grant (SP1861/0401) to R Callaghan. The authors would like to thank J. Ryland and D. Mullins their patience and inspiration in the early stages.