Comparison of the Blood-Brain Barrier Transport and Vulnerability to P-Glycoprotein-Mediated Drug-Drug Interaction of Domperidone versus Metoclopramide Assessed Using In Vitro Assay and PET Imaging.

ABSTRACT: Domperidone and metoclopramide are widely prescribed antiemetic drugs with distinct neurological side effects. The impact of P-glycoprotein (P-gp)-mediated efflux at the blood-brain barrier (BBB) on brain exposure and BBB permeation was compared in vitro and in vivo using positron emission tomography (PET) imaging in rats with the radiolabeled analogs [¹¹C]domperidone and [¹¹C]metoclopramide. In P-gp-overexpressing cells, the IC₅₀ of tariquidar, a potent P-gp inhibitor, was drastically different using [¹¹C]domperidone (221 nM [198-248 nM]) or [¹¹C]metoclopramide (4 nM [2-8 nM]) as the substrate. Complete P-gp inhibition led to a 1.8-fold higher increase in the cellular uptake of [¹¹C]domperidone compared with [¹¹C

SUBMITTER: Breuil L 

PROVIDER: S-EPMC9412994 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature