Participation of monocarboxylate transporter 8, but not P-glycoprotein, in carrier-mediated cerebral elimination of phenytoin across the blood-brain barrier

Intracerebral pre-administration of unlabeled phenytoin attenuated blood-brain barrier (BBB)-mediated phenytoin efflux transport. Preadministration of P-glycoprotein (P-gp) substrates in rats and genetic P-gp deficiency in mice did not affect BBB-mediated phenytoin efflux transport. In contrast, pre-administration of monocarboxylate transporter-8 (MCT8) inhibitors attenuated phenytoin efflux. Our data suggest that MCT8 at the BBB participates in phenytoin efflux transport from the brain to the blood.