Phenytoin transport in epileptic brain is mediated by RLIP76. A-B) Relative contribution of RLIP76 and MDR1 to total AED transport capacity in IOV prepared from brain tissue of non-epileptic, non-multiple drug resistant and multiple drug resistant epileptic patients. This was determined using anti-RLIP76 and anti-MDR1 antibodies [23,25]. In this figure, * and ** represent p < 0.05 and 0.01 respectively. C-D) Time dependent PHE uptake by IOV prepared from primary cultures of astrocytes or endothelial cells from normal (diamonds) or epileptic brain (squares). E-F) Brain PHE levels in RLIP76+/+ and RLIP76-/- mice 2 h after IP administration of Phosphenytoin at 33 or 83 mg/kg (3 animals/group). G) After exposure to the antiepileptic drug, RLIP76+/+ animals (left panel) appeared relatively unaffected compared with RLIP76-/- mice (right panel) where a severe neurological toxicity including extensor posturing, lethargy and status epilepticus were observed.