In vitro concentration dependent transport of phenytoin and phenobarbital, but not ethosuximide, by human P-glycoprotein

Abstract

Aims: One possible mechanism for epilepsy drug resistance is overexpression of P-glycoprotein in the blood-brain barrier, but whether (or which) antiepileptic drugs (AEDs) are transported by P-gp remains unclear. We evaluated AEDs as P-gp substrates using cell monolayers. Main methods: Bi-directional transport assays and concentration equilibrium transport assays (CETAs) were performed for phenytoin (PHT), phenobarbital (PB), and ethosuximide (ESM) using wildtype Madin-Darby Canine Kidney II cell line MDCKII and porcine renal endothelial cell line LLC-PK1 cells and these cells transfected with human MDR1 cDNA to express P-gp. Key findings: Wildtype cells demonstrated no efflux transport of P..