In vitro concentration dependent transport of phenytoin and phenobarbital, but not ethosuximide, by human P-glycoprotein
Chunbo Zhang, Patrick Kwan, Zhong Zuo, Larry Baum
LIFE SCIENCES | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2010
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..View full abstract
Awarded by CUHK
Cell lines were kindly provided by Prof. P. Borst, The Netherlands Cancer Institute. Financial support was provided by CUHK Direct Grant 2008.1.078.