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J Cereb Blood Flow Metab. 2015 May;35(5):743-6. doi: 10.1038/jcbfm.2015.19. Epub 2015 Feb 11.

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

Author information

1
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
2
Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
3
Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
4
1] Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria [2] Department of Pharmacology, Toxicology and Pharmacy, Center for Systems Neuroscience, University of Veterinary Medicine, Hannover, Germany.
5
1] Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria [2] Health and Environment Department, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
6
Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
7
1] Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria [2] Medical Imaging Cluster, Medical University of Vienna, Vienna, Austria.
8
1] Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria [2] Health and Environment Department, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria [3] Medical Imaging Cluster, Medical University of Vienna, Vienna, Austria.

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 (VT) 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 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.

PMID:
25669913
PMCID:
PMC4420865
DOI:
10.1038/jcbfm.2015.19
[Indexed for MEDLINE]
Free PMC Article

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