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.
Publication types
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Clinical Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B / antagonists & inhibitors
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ATP Binding Cassette Transporter, Subfamily B / metabolism
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Anti-Arrhythmia Agents / administration & dosage
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Blood-Brain Barrier* / diagnostic imaging
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Blood-Brain Barrier* / metabolism
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Carbon Isotopes / administration & dosage
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Gray Matter* / diagnostic imaging
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Gray Matter* / metabolism
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Humans
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Male
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Middle Aged
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Pituitary Gland* / diagnostic imaging
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Pituitary Gland* / metabolism
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Positron-Emission Tomography
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Radiography
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Radiopharmaceuticals / administration & dosage*
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Verapamil / administration & dosage*
Substances
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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Anti-Arrhythmia Agents
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Carbon Isotopes
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Radiopharmaceuticals
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Verapamil