Participation of Monocarboxylate Transporter 8, But Not P-Glycoprotein, in Carrier-Mediated Cerebral Elimination of Phenytoin across the Blood-Brain Barrier.

ABSTRACT:

Purpose

In this study, we investigated in detail the transport of phenytoin across the blood-brain barrier (BBB) to identify the transporter(s) involved in BBB-mediated phenytoin efflux from the brain.

Methods

We evaluated the brain-to-blood efflux transport of phenytoin in vivo by determining the brain efflux index (BEI) and uptake in brain slices. We additionally conducted brain perfusion experiments and BEI studies in P-glycoprotein (P-gp)-deficient mice. In addition, we determined the mRNA expression of monocarboxylate transporter (MCT) in isolated brain capillaries and performed phenytoin uptake studies in MCT-expressing Xenopus oocytes.

Results

[¹⁴C]Phenytoin brain efflux was time-dependent with a half-life of 17 min in rats and 31 min in mice. Intrac

SUBMITTER: Jomura R 

PROVIDER: S-EPMC8906351 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature