Approaching complete inhibition of P-glycoprotein at the human blood-brain barrier: An (R)-[11 C]verapamil PET study

Martin Bauer, Rudolf Karch, Markus Zeitlinger, Cécile Philippe, Kerstin Römermann, Johann Stanek, Alexandra Maier-Salamon, Wolfgang Wadsak, Walter Jäger, Marcus Hacker, Markus Müller, Oliver Langer

    Publications: Contribution to journalArticlePeer Reviewed

    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.

    Original languageEnglish
    Pages (from-to)743-746
    Number of pages4
    JournalJournal of Cerebral Blood Flow and Metabolism
    Volume35
    Issue number5
    DOIs
    Publication statusPublished - 5 May 2015

    Austrian Fields of Science 2012

    • 301207 Pharmaceutical chemistry

    Keywords

    • (R)-[11C]verapamil
    • blood-brain barrier
    • P-glycoprotein
    • pituitary gland
    • positron emission tomography
    • tariquidar

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