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

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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Brief Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420865/
https://www.ncbi.nlm.nih.gov/pubmed/25669913
http://dx.doi.org/10.1038/jcbfm.2015.19
Descripción
Sumario: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.

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