Approaching Complete Inhibition of P-Glycoprotein at the Human Blood–Brain Barrier: An (R)-[11C]Verapamil PET Study. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Bauer, Martin; Karch, Rudolf; Zeitlinger, Markus; Philippe, Cécile; Römermann, Kerstin; Stanek, Johann; Maier-Salamon, Alexandra; Wadsak, Wolfgang; Jäger, Walter; Hacker, Marcus; Müller, Markus; Langer, Oliver
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 35:Issue 5(2015)
• Page Start: 743
• Page End: 746
• Publication Date: 2015-05
• Subjects: blood–brain barrier; -- P-glycoprotein; -- pituitary gland; -- positron emission tomography; -- (R)-[11C]verapamil -- tariquidar; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1038/jcbfm.2015.19
• Languages: English
• ISSNs: 0271-678X

Abstract

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 )-[ 11 C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume ( V T ) of ( R )-[ 11 C]verapamil in whole-brain gray matter increased by 273 ± 78% relative to baseline scans without tariquidar, which was higher than previously reported V T increases. During tariquidar infusion whole-brain V T was comparable to V T in the pituitary gland, a region not protected by the BBB, which suggested that we were approaching complete Pgp inhibition at the human BBB.