Epilepsy Research (2014) 108, 359—366 jo ur nal ho me p ag e: www.elsevier.com/locate/epilepsyres In vitro transport assays of rufinamide, pregabalin, and zonisamide by human P-glycoprotein Pui Shan Chan a , Chunbo Zhang a,1 , Zhong Zuo a , Patrick Kwan b,c , Larry Baum a,* a School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong, China b Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China c Department of Medicine and Neurology, The University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia Received 9 November 2012; received in revised form 13 January 2014; accepted 20 January 2014 Available online 30 January 2014 KEYWORDS Pgp; ABCB1; MDR1; Rufinamide; Zonisamide; Pregabalin Summary Objective: Epilepsy is resistant to treatment with antiepileptic drugs (AEDs) in about one third of epilepsy patients. AED export by P-glycoprotein (Pgp) overexpressed in the blood—brain barrier may contribute to AED resistance. The Pgp transport status of many of the recently approved AEDs remains unknown. We investigated whether several new AEDs — zonisamide (ZNS), pregabalin (PGB), and rufinamide (RFM) — are human Pgp substrates. Methods: MDCKII and LLC-PK1 cells transfected with the human MDR1 gene, which encodes the Pgp protein, were used in concentration equilibrium transport assays (CETA) to determine the substrate status of ZNS, PGB, and RFM. For each drug, an equal concentration was added to apical and basal chambers, and the concentration in both chambers was measured up to 4 h. Results: RFM, ZNS, and PGB were not transported by MDR1-transfected cells from basolateral to apical sides in CETA. Conclusions: ZNS, RFM, and PGB are not substrates of human Pgp. These data suggest that resistance to these drugs may not be attributed to increased Pgp activity in resistant patients. © 2014 Elsevier B.V. All rights reserved. ∗ Corresponding author. Tel.: +852 39436833; fax: +852 26035295. E-mail address: lwbaum@cuhk.edu.hk (L. Baum). 1 Current address: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30606, USA. Introduction Despite the development of over 20 antiepileptic drugs (AEDs), epilepsy does not respond to AED treatment in approximately one third of patients, due to mechanisms that remain unclear (Kwan and Brodie, 2000). The ABCB1 0920-1211/$ — see front matter © 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.eplepsyres.2014.01.011