title: In vitro transport assays of rufinamide, pregabalin, and zonisamide by human P-glycoprotein.
abstract: 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 4h.
  
  
  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.
authors: School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors: Pui Shan
authors: PS
authors: Chan
authors: School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors: Chunbo
authors: C
authors: Zhang
authors: School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors: Zhong
authors: Z
authors: Zuo
authors: Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Department of Medicine and Neurology, The University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia.
authors: Patrick
authors: P
authors: Kwan
authors: School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong, China. Electronic address: lwbaum@cuhk.edu.hk.
authors: Larry
authors: L
authors: Baum
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects; D002461:Cell Line, Transformed; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007555:Isoxazoles / Q000378:metabolism / Q000493:pharmacokinetics; D000069583:Pregabalin; D020112:Rhodamine 123 / Q000378:metabolism; D013552:Swine; D014162:Transfection; D014230:Triazoles / Q000493:pharmacokinetics; D000078305:Zonisamide; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D007555:Isoxazoles; D014230:Triazoles; D020112:Rhodamine 123; D000078305:Zonisamide; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; C079703:rufinamide
keywords: ABCB1; MDR1; Pgp; Pregabalin; Rufinamide; Zonisamide