Neuropharmacokinetic interaction between antiepileptic drugs

Abstract

The hypothesis was that the co-administration of two or more antiepileptic drugs would lead to neuropharmacokinetic interactions in the brain. To test the hypothesis, microdialysis and jugular vein cannulation technique were used to obtain rat brain extracellular fluid and plasma samples following intra-peritoneal administration of antiepileptic drugs (AEDs) given alone or in combination at low and high doses. Phenytoin, felbamate and carbamazepine were chosen as the model drugs. A combined administration of AEDs at the low dose did not significantly affect their bioavailability in brain as well as in plasma, whereas that at the higher dose enhanced significantly their brain bioavailability even though the plasma concentrations of the AEDs still remained the same compared to their respective levels when given alone. The overall findings of this study suggest that at a certain non-toxic dose, co-administration of the AEDs caused neuropharmacokinetic drug interactions, possibly through modulation on brain drug transporter activities.