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Approaching Complete Inhibition of P-Glycoprotein at the Human Blood–Brain Barrier: An (R)-11CVerapamil PET Study
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Approaching Complete Inhibition of P-Glycoprotein at the Human Blood–Brain Barrier: An (R)-11CVerapamil PET Study
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Journal Article
Approaching Complete Inhibition of P-Glycoprotein at the Human Blood–Brain Barrier: An (R)-11CVerapamil PET Study
2015
Overview
As P-glycoprotein (Pgp) inhibition at the blood–brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate (R)-[11C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume (VT) of (R)-[11C]verapamil in whole-brain gray matter increased by 273 ± 78% relative to baseline scans without tariquidar, which was higher than previously reported VT increases. During tariquidar infusion whole-brain VT was comparable to VT in the pituitary gland, a region not protected by the BBB, which suggested that we were approaching complete Pgp inhibition at the human BBB.
Publisher
SAGE Publications,Sage Publications Ltd,Nature Publishing Group
Subject
Anti-Arrhythmia Agents - administration & dosage
/ ATP Binding Cassette Transporter, Subfamily B - antagonists & inhibitors
/ ATP Binding Cassette Transporter, Subfamily B - metabolism
/ Blood-Brain Barrier - diagnostic imaging
/ Blood-Brain Barrier - metabolism
/ Carbon Isotopes - administration & dosage
/ Gray Matter - diagnostic imaging
/ Humans
/ Male
/ Pituitary Gland - diagnostic imaging
/ Pituitary Gland - metabolism
/ Positron-Emission Tomography
