Impact of P-Glycoprotein Function on the Brain Kinetics of the Weak Substrate ¹¹C-Metoclopramide Assessed with PET Imaging in Humans.

ABSTRACT: PET with avid substrates of P-glycoprotein (ABCB1) provided evidence of the role of this efflux transporter in effectively restricting the brain penetration of its substrates across the human blood-brain barrier (BBB). This may not reflect the situation for weak ABCB1 substrates including several antidepressants, antiepileptic drugs, and neuroleptics, which exert central nervous system effects despite being transported by ABCB1. We performed PET with the weak ABCB1 substrate ¹¹C-metoclopramide in humans to elucidate the impact of ABCB1 function on its brain kinetics. Methods: Ten healthy male subjects underwent 2 consecutive ¹¹C-metoclopramide PET scans without and with ABCB1 inhibition using cyclosporine A (CsA). Pharmacokinetic modeling was performed to estim

SUBMITTER: Tournier N 

PROVIDER: S-EPMC6604692 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature