title: Approaching complete inhibition of P-glycoprotein at the human blood-brain barrier: an (R)-[11C]verapamil PET study.
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.
authors: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors: Martin
authors: M
authors: Bauer
authors: Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
authors: Rudolf
authors: R
authors: Karch
authors: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors: Markus
authors: M
authors: Zeitlinger
authors: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
authors: Cécile
authors: C
authors: Philippe
authors: 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.
authors: Kerstin
authors: K
authors: Römermann
authors: 1] Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria [2] Health and Environment Department, AIT Austrian Institute of Technology GmbH, Seibersdorf, Austria.
authors: Johann
authors: J
authors: Stanek
authors: Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
authors: Alexandra
authors: A
authors: Maier-Salamon
authors: 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.
authors: Wolfgang
authors: W
authors: Wadsak
authors: Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
authors: Walter
authors: W
authors: Jäger
authors: 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.
authors: Marcus
authors: M
authors: Hacker
authors: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors: Markus
authors: M
authors: Müller
authors: 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.
authors: Oliver
authors: O
authors: Langer
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism; D002247:Carbon Isotopes / Q000008:administration & dosage; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography; D011859:Radiography; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D014700:Verapamil / Q000008:administration & dosage*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000889:Anti-Arrhythmia Agents; D002247:Carbon Isotopes; D019275:Radiopharmaceuticals; D014700:Verapamil