Approaching Complete Inhibition of P-Glycoprotein at the Human Blood–Brain Barrier: An (R)-[11C]Verapamil PET Study-Reference-Cited by-同舟云学术

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

Published:2015-02-11 Issue:5 Volume:35 Page:743-746
ISSN:0271-678X
Container-title:Journal of Cerebral Blood Flow & Metabolism
language:en
Short-container-title:J Cereb Blood Flow Metab

Author:

Bauer Martin¹,Karch Rudolf²,Zeitlinger Markus¹,Philippe Cécile³,Römermann Kerstin¹⁴,Stanek Johann¹⁵,Maier-Salamon Alexandra⁶,Wadsak Wolfgang³⁷,Jäger Walter⁶,Hacker Marcus³⁷,Müller Markus¹,Langer Oliver¹⁵⁷

Affiliation:

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. Department of Pharmacology, Toxicology and Pharmacy, Center for Systems Neuroscience, University of Veterinary Medicine, Hannover, Germany

5. 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. 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)-[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

Subject

Cardiology and Cardiovascular Medicine,Clinical Neurology,Neurology

Link

http://journals.sagepub.com/doi/pdf/10.1038/jcbfm.2015.19

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