Potential role for human P-glycoprotein in the transport of lacosamide

Abstract

Purpose Antiepileptic drugs (AEDs) do not effectively treat 30-40% of patients with epilepsy. Export of AEDs by P-glycoprotein (Pgp, ABCB1, or MDR1), which is overexpressed in the blood-brain barrier in drug-resistant patients, may be a mechanism for resistance to AEDs. For most recently approved AEDs, whether they are transported by Pgp is unknown. We investigated whether a new AED, lacosamide (LCM), is a substrate of human Pgp. Methods LLC-PK1 and MDCKII cells transfected with the human MDR1 gene were used to determine the substrate status of LCM in concentration equilibrium transport assays (CETAs). An equal concentration of drug was initially loaded in both the apical and basal chambers,..