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

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


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

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Anti-Arrhythmia Agents / administration & dosage
  • Blood-Brain Barrier* / diagnostic imaging
  • Blood-Brain Barrier* / metabolism
  • Carbon Isotopes / administration & dosage
  • Gray Matter* / diagnostic imaging
  • Gray Matter* / metabolism
  • Humans
  • Male
  • Middle Aged
  • Pituitary Gland* / diagnostic imaging
  • Pituitary Gland* / metabolism
  • Positron-Emission Tomography
  • Radiography
  • Radiopharmaceuticals / administration & dosage*
  • Verapamil / administration & dosage*


  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Anti-Arrhythmia Agents
  • Carbon Isotopes
  • Radiopharmaceuticals
  • Verapamil